Neuropathy+vision Loss

Dr. Jason Lawrence Meyer is a chiropractor who runs the World of Wellness Chiropractic Offices in Fort Worth and Arlington, TX. wowhealthcenters Integrative medicine which is also called integrated medicine or integrative health, combines alternative medicine with evidencebased medicine. Proponents claim that it treats the whole person , focuses on wellness and health rather than on treating disease, and emphasizes the patientphysician relationship. The Defining Principles of Integrative Medicine 1. Patient and practitioner are partners in the healing process. 2. All factors that influence health, wellness, and disease are taken into consideration,.

Including mind, spirit, and community, as well as the body. 3. Appropriate use of both conventional and alternative methods facilitates the body’s innate healing response. 4. Effective interventions that are natural and less invasive should be used whenever possible. 5. Integrative medicine neither rejects conventional medicine nor accepts alternative therapies uncritically. 6. Good medicine is based in good science. It is inquirydriven and open to new paradigms. 7. Alongside the concept of treatment, the broader concepts of health promotion and the prevention of illness are paramount. 8. Practitioners of integrative medicine should exemplify its principles and commit themselves.

To selfexploration and selfdevelopment. World of wellness is a group of medical offices specializing in functional medicine, natural wellness and prevention. We offer integrated services providing fabulous bodywork in a fun and upbeat environment. our highly trained staff including Dr. Jason Meyer DC offer services such as natural medicine, pain relief, rehabilitation, therapy, massage, weightloss, nutrition, allergy testing, allergy management, arthritis relief, pain management, headache relief, and more, our mission statement and corporate purpose is to help people in the country become happier and healthier through natural healthcare. We are fully staffed with medical doctors,.

Nurse practitioners, chiropractors such as Dr. Jason Lawrence Meyer and licensed massage therapists and we are dedicated to help you obtain optimum wellness. Have you explored the World of wellness Fort Worth functional medicine World of Wellness would like to show you how optimizing your health and wellness can, in turn, eliminate any chronic pain that you may suffer from. Dr. Jason Meyer and Our team invites you to pay us a visit at our Fort Worth natural wellness clinic, where you will receive focused attention from a whole team of medical professionals.

We pride ourselves in working closely with each patient, explaining to them the potential sources of their pain and how that pain can be eliminated. World of Wellness provides Fort Worth and Arlington wellness and prevention that helps hold off chronic pain. Through our allnatural methods, we are able to treat a wide variety of ailments, including, but certainly not limited to Low back pain Migraine headaches Sciatica Neuropathy Neck pain Sports injuries Allergies Weight loss What makes our Fort Worth Chiropractic and functional medicine so effective is that we use natural methods of treatment instead of introducing harsh chemicals or subjecting.

The body to painful surgical procedures. Prescription medication might take away your pain, but not without a price. Many of these powerful medications can cause damage to other parts of your body. This is why our wellness clinic in Fort Worth shies away from using these drugs. The experienced staff at our functional medicine clinic in Fort Worth TX is truly unique. We staff a whole team of medical professionals who specialize in various areas of health and wellness. This means all of our resources are together under one roof. Many traditional.

Doctors will refer patients to other specialists because they are not equipped to handle certain treatments. Keeping our patients in one facility ensures strong communication and lets you garner the advantages of working with an entire team of professionals rather than just one doctor. We want to meet with you and open your eyes to a new way of reducing or eliminating your chronic pain. World of Wellness offers free consultation appointments. Make an appointment now and see what our Fort Worth functional medicine methods can do for you. Dr. Jason Meyer D.C. Jason Meyer Chiropractor.

Accessibility at WIU Accessible Documents

Accessibility at WIU Accessible Documents Hi, my name is Matthew Lawson, I am a freshman meteorology major at Western Illinois University. My vision impairment is leber’s hereditary optic neuropathy, I cannot see distance, I cannot read fine print. It started when I was fifteen years old and decreased six to eight months later. Technology I use for education, I use what’s called Jaws, it is a screen reader. It reads everything off the computer anything that you type Jaws speaking type anything that you do, it reads it for you.

Chronic Sinusitis, Dizziness, EarEye Pain, Abnormal Hearing, Smelling, Taste, Touch Migraine

When you hear someone say they get migraines, you probably think of headaches, really BAD headaches. But in fact, the symptoms associated with migraine neuropathy are widely varied. What can some of those symptoms feel like It felt like my skull couldn’t accommodate the balloon that someone was blowing up inside of my head. Instead of just the sensitivity to light, I was now getting sensitivity to sound and to feeling. What it feels like in my ears is pain and pressure that radiates to my eye and down to the joint below my ear and into my jaw.

I had problems driving on the highway where I felt like I couldn’t keep track of the road, like it seemed like the road was kind of going away from me. There is a family history with migraines in the family, mainly the women. And the one time that I had a migraine so severely they did not know if it was a migraine or a stroke. Very scary situation.. The spinning sensation occurred whenever I moved my head. Even slight movement like this or like this. There’s a squishiness in my ear that never leaves, and I also noticed that I smell things.

That other people don’t smell and I taste things that are have a odd taste to them, that are not recognized by others. I would pull into my driveway, get out of the car, and I would even have a feeling that I was still moving or I would look at the car and think maybe my car was still rolling. I did recently find out that aphasia could be an aspect of this atypical migraine symptom, and my husband and I almost have a joke about it. I’ll be speaking, and I’ll just raise.

My eyebrows and point to him, and he’ll say the word I can’t find. Almost every time I went to the doctor’s, I was given an antibiotic and I was also given a slip to have a CAT scan. I am still left with the same problems, the same ear pain, the same pressure, the same vestibular disturbance. The antibiotics did nothing. I believe I’ve seen three or four different Ear, Nose, and Throat Doctors who have sent me for Xrays, MRIs, CAT scans I’m not sure what all tests, but they’ve all come back negative.

By chance he said, Have you tried magnesium First I was so surprised that he was taking me seriously, that I just started to laugh. I’ve been on the Topamax now for 6 months and I’ve had no sinus symptoms whatsoever. And I can’t tell you how much that has changed my life. So it got to the point where I can wear socks, I don’t have to think twice of which is the worst bra, which is the best bra. I can actually get dressed, um, the sensitivity is I would say 95 gone.

Mitochondria dynamic organelles critical for human health

IT’S A REAL PLEASURE TO HAVE PROFESSOR DAVID CHAN HERE. HE IS PROFESSOR OF THE DIVISION OF BIOLOGY AND ALSO AN INVESTIGATOR AT THE HOWARD HUGHES MEDICAL INSTITUTE AT CALIFORNIA INSTITUTE OF TECHNOLOGY. HE GOT HIS MD AND Ph.D. IN HST PROGRAM AT HARVARD AND MIT AND AFTER THAT, HIS POSTDOC RECALL WORK AT THE WHITEHEAD INSTITUTE. AND THEN JOINED THE CALIFORNIA INSTITUTE OF TECHNOLOGY BACK IN 2000 WHERE HE IS ASSEMBLED HE IS WORLDKNOWN AS AN EXPERT IN BOTH MITOCHONDRIAL DYNAMICS AS WELL AS MITOCHONDRIAL DNA PROTECTION AND PROCESSING.

IT’S A FIELD THAT IS EXPANDING. WE WERE JUST CHATTING BECAUSE OF THE IMPACT IN CELL BIOLOGY AND POINT OF FACT, MUCH OF THE WORK THAT PROFESSOR CHAN HAS LED TO THE IMPORTANCE OF THIS ORGANELLE IN THE FUNCTIONING OF THE SELL. WE LOOK FORWARD TO YOUR PRESENTATION. gtgt SO I’M REALLY GRATEFUL FOR THE INVITATION TO COME AND SPEAK HERE. I HAD A GREAT TIME MEETING WITH INVESTIGATORS HERE AT NIH AND HEARING ABOUT THEIR VERY INTERESTING WORK. SO MY LAB IS INTERESTED IN THE DYNAMIC PROPERTIES OF MITOCHONDRIA. SO FIRST I WANT TO GO THROUGH.

SOME OF THE WAYS IN WHICH MIGHT QUANDARY ARE DYNAMIC MITOCHONDRIA ARE DYNAMIC. MITOCHONDRIA UNDERGO CYCLES OF FUSION AND FISSION. YOU CAN HAVE TWO MITOCHONDRIA THAT COME ITSELF AND FUSE SO THAT THERE IS ONLY ONE MITOCHONDRIA AND AT THE SAME TIME, YOU VEHICLE THE OPPOSITE PROCESS WHERE A HEIGHT QUANDARYIA DIVIDES BY FISSION INTO TWO SMALLER ORGANELLES. ANOTHER WAY IN WHICH MITOCHONDRIA ARE DYNAMIC, IS THEY ARE TRANSPORTED TO SPECIFIC PARTS OF THE CELL AND THIS OCCURS ALONG THE CYTOSKELETON. SO, FOR EXAMPLE, YOU CAN HAVE MOVEMENT AWAY FROM THE CELL.

NUCLEUS AND RETRO GRADE MOVEMENT TOWARDS THE CELL NUCLEUS. AND IN CERTAIN CELL TYPES, THIS HELPS TO DISTRIBUTE THE MITOCHONDRIA IN THE CELL. BUT IN CERTAIN SPECIALIZED CELL TYPES LIKE NEURONS, THIS CAN REALLY LOCALIZE MIGHT MITOCHONDRIA TO SPECIFIC SUB CELLULAR SITES. SO FOR EXAMPLE NNEURONS THIS TYPE OF ACTIVE TRANSPORT HELPS TO ENSURE THAT MITOCHONDRIA ARE WELL RESPECTED AT THE TERM IN THIS WHERE THEY PLAY IMPORTANT ROLLS IN ATP PRODUCTION AND CALCIUM. AND PARTICULARLY I THINK A DRAMATIC EXAMPLE IS SHOWN IN JEFF’S WORK AT HARVARD WHERE THIS IS A TRANSGENIC MOUSE THAT.

EXPRESSES A MIGHT MITOCHONDRIALY TARGETED MOLECULE AND YOU CAN SEE INDIVIDUAL MITOCHONDRIA IN THIS PART OF THE NERVE. WHEN THE MOTOR NEURONS TERMINATE AT THE MOTOR END PLATE, WHICH IS HIGHLIGHTED IN RED, YOU CAN SEE THAT THE MITOCHONDRIA ARE SO DENSE THAT YOU CAN’T MAKE OUT INDIVIDUAL ORGANELLES. SO THIS IS AN EXAMPLE OF HOW ACTIVE TRANSPORT CAN SERVE TO LOCALIZE MITOCHONDRIA TO SPECIFIC PARTS OF THE CELL. ANOTHER WAY IN WHICH MITOCHONDRIA ARE DYNAMIC, THEY UNDERGO CONDUCT RECALL CHANGES IN APOPTOSIS. SO THEY 81 TAIN TWO MEMBRANES. AN OUTER MEMBRANE AND A INNER.

MEMBRANE AND THE INNER MEMBRANE IS CONVOLUTED INTO THESE COMPARTMENTS. SO IT’S ARGUED THAT CONTENTS OF THE MEMBRANE ARE NOT DIFFUSIBLE AND YOU HAVE TO OPEN UP THESE CRICETID JUNCTIONS IN ORDER FOR THESE CONTENTS TO BE INTERACTING WITH EACH OTHER. AND DURING THE PROCESS OF APOPTOSIS, IN MANY CASES, THERE IS FRAGMENTATION OF MITOCHONDRIA SO THERE IS INDUCED MITOCHONDRIAL VISION, WHICH LEADS TO MITOCHONDRIAL FRAGMENTATION. THERE IS OPENING OF THE MITOCHONDRIAL OUTER MEMBRANES AND THERE IS ALSO CHANGES IN THE CRICETID JUNCTIONS SO THAT INTERMEMBRANE COMPONENTS CAN COME OUT AND THEY PLAY.

PROAPOPTOTIC ROLLS. FINALLY, THE LAST DYNAMIC FEATURE OF MITOCHONDRIA I WANTED TO POINT OUT IS THAT THEY UNDERGO SELECTIVE DEGRADATION BY AWE TO HAVE GHEE. THAT IS A TERM AWE TO HAVE GEE. THIS IS WORK FROM JOHN’S GROUP WHERE HE SHOWS USING MOUSE HEPATOCYTES THAT YOU CAN HAVE DAMAGE MITOCHONDRIAL UNDERGOING DEGRADATION. SO THESE RED SPOTS HERE ARE THE MITOCHONDRIA IN THESE HEPATOCYTES AND A LASER IS USED TO INACTIVATE THE MEMBRANE POTENTIAL IN SOME OF THESE MITOCHONDRIA AND THOSE MITOCHONDRIA ARE THE ONES THAT THEN ASSOCIATE WITH AN AWE TO.

HAVE GEE MARKER. LET ME GO BACK AND TALK ABOUT FUSION AND DIVISION. SO, INHERENTLY THIS IS A SOMEWHAT COMPLICATED PROCESS BECAUSE MITOCHONDRIA HAVE DOUBLE MEMBRANES. AND SO, DURING THE PROCESS OF MITOCHONDRIAL FUSION, THERE HAS TO BE COORDINATED FUSION OF FOUR LIPID BILAYERS, SO TWO OUTER MEMBRANES AND TWO INNER MEMBRANES AND THE NET RESULT OF THIS FUSION EVENT IS THAT THERE IS LIPID MIXING BETWEEN THESE TWO MEMBRANES AND CONTENT MIXING SO THAT THE CONTENT OF THE INTERIM MEMBRANE SPACE ARE MIXED AND THE CONTENTS OF THE MATRIX, THE INTERNAL CONTENT OF THE.

MITOCHONDRIA ARE MIXED. AND THIS PROCESS TURNS OUT TO BE DEPENDENT ON MEMBRANE POTENTIAL ACROSS THE INNER MEMBRANE. AND THERE ARE MANY FUNCTIONS OF MITOCHONDRIAL FUSION AND FISSION, WHICH I’LL TALK MORE ABOUT. BUT ONE OF THE FUNCTIONS IS THAT IT CONTROLS THE MORPHOLOGY OF MITOCHONDRIA. SO THE BALANCE BETWEEN FUSION AND FISSION CONTROLS MITOCHONDRIAL SHAPE, SIZE AND NUMBER. SO, THE MOLECULES THAT ARE INVOLVED IN MITOCHONDRIAL FUSION TURN OUT TO BE LARGE GTPPASES AND THERE ARE THREE IN MAMMALS. SO OUR WORK HAS FOCUSED ON MAMMALIAN CELLS AND THESE ARE.

SOME GROUPS THAT WORK ON SIMILAR PROBLEMS IN YEAST CELLS. SO IN MAMMALS, THERE ARE TWO SETS OF LARGE GTPPASES. THE FIRST TWO ARE MFM1 AND 2. THESE ARE OUTER MEMBRANE GTPPASES THAT HAVE A USHAPED TRANSMEMBRANE DOMAIN AND THEY ARE NECESSARY FOR MITOCHONDRIAL FUSION. SO MICE THAT ARE DEFICIENT FOR MFM1 OR 2 HAVE FRAGMENTED MITOCHONDRIA SO THE GREEN SPOTS OVER HERE ARE FRAGMENTED MITOCHONDRIA AND MFM DEFICIENT CELLS IN CONTRAST TO THE TUBULAR PRESENT IN WILDTYPE CELLS. AND AGAIN, THIS REITERATES THE FACT THAT WHEN YOU HAVE REDUCED MITOCHONDRIAL FUSION THERE IS.

STILL ONGOING MITOCHONDRIAL DIVISION AND THAT LEADS TO MITOCHONDRIAL FRAGMENTATION. SO THE BALANCE BETWEEN FUSION AND FISSION CONTROLS MITOCHONDRIAL SIZE, SHAPE AND NUMBER. IN ADDITION TO THE MIGHT FUSIONS LOCATED ON THE MITOCHONDRIAL OUTER MEMBRANE, THERE IS ALSO OPAL 1, A PROTEIN LOCALIZED TO THE MITOCHONDRIAL INNER MEMBRANE. THIS PROTEIN IS ALSO ESSENTIAL FOR MITOCHONDRIAL FUSION. SO CELLS THAT LACK OPAL 1 HAVE NO DETECTABLE MITOCHONDRIAL FUSION. AND BY USING MOUSE KNOCKOUS AND GENERATING CELL LINES FROM THOSE MOUSE KNOCKOUTS, WE CAN LOOK AT THE SELECTIVE ROLES OF MITOFUSEINS AND OPA1.

SO BOTH OF THESE CELLS ARE DEFICIENT FOR FULL MITOCHONDRIAL FUSION BUT IF YOU LOOK MORE SPECIFICALLY AT OUTER MEMBRANE FUSION VERSUS INNER MEMBRANE FUSION, THEY HAVE A DIFFERENCE. SO MIGHT ON FUSEINS LOCATED ON THE OUTER MEMBRANE ARE DEFECTIVE FOR OUTER MEMBRANE FUSIONS. THEY DON’T UNDERGO THE FIRST STEPS. WHEREAS IN OPA1 DEFICIENT CELLS THOSE CELLS WILL UNDERGO OUTER MEMBRANE FUSION BUT THEY GET TRAPPED AT THIS INTERMEDIATE AGE AND SO THEY ARE UNABLE TO UNDERGO INNER MEMBRANE FUSION. SO WE CURRENTLY VIEW MITOCHONDRIAL FUSION AS A MULTISTEP PROCESS WHERE OUTER.

MEMBRANE FUSION OCCURS FIRST. THIS DEPENDS ON MITOFUSE INS LOCATED ON THE OUTER MEMBRANE FOLLOWED BY INNER MEMBRANE FUSION WHICH IS DEPENDENT ON OPA1, WHICH IS EITHER THERE IS AN ISOFORM ASSOCIATED WITH THE INNER MEMBRANE AND OTHERS THAT ARE IN THE INTERMEMBRANE SPACE. SO I MENTIONED THAT MITOCHONDRIAL FUSION CONTROL MITOCHONDRIAL MORPHOLOGY. AN EXAMPLE IS SHOWN HERE. SO IN THE NORMAL FIBROBLASTS, YOU HAVE NORMAL RATES OF MITOCHONDRIAL FUSION AND FISSION. HERE IS A FIBROBLAST. THE BLANK AREA HERE IS THE NUCLEUS AND YOU CAN SEE IT HAS TUBULAR MITOCHONDRIA.

IF YOU KNOCKOUT PROTEINS INVOLVED IN MITOCHONDRIAL FUSION LIKE MFNs THERE IS LOWER LEVELS OF MITOCHONDRIAL FUSION WHICH NEEDS TOMMIED MITOCHONDRIAL FRAGMENTATION. YOU CAN DO THE OPPOSITE EXPERIMENT AND BLOCK FISSION IN THESE CELLS AND IN THAT CASE, YOU GET CELLS THAT HAVE OVERLY LONG AND INTERCONNECTED MITOCHONDRIA. YOU CAN ALSO SIMULTANEOUSLY BLOCK MITOCHONDRIAL FUSION AND FISSION AND WHEN YOU DO THAT, YOU CAN RESTORE MITOCHONDRIAL TUBUALS TO THESE CELLS THAT HAVE FRAGMENTED MITOCHONDRIA. THIS IS AN EXAMPLE OF HOW TO MANIPULATE THE MORPHOLOGY OF MITOCHONDRIA BY MANIPULATING THE BALANCE BETWEEN FUSION AND.

FISSION. NOW, ONE OF THE REASONS THAT WE ARE INTERESTED IN THESE PROCESSES IS THAT HUMAN GENETIC STUDIES INDICATE THAT THESE PROCESSES ARE CLEARLY IMPORTANT FOR HUMAN HEALTH. SO THE FIRST DISEASE THAT ILLUSTRATES THIS IS DOMINANT OPTIC ATROPHY. WHICH IS THE MOST COMMONLY INHERITED OPTIC NEUROPATHY CAUSED BY HETEROZYGOUS MUTATIONS IN OPA1. SO IN THIS DISEASE, THERE IS DEGENERATION OF THE RETINAL GANG RIA CELLS, WHICH HAVE CELL BODIES THAT ARE LOCATED IN THE RETINA AND THEIR PROCESSES ARE BUNDLED INTO THE OPTIC NERVE. AND SO THIS IS A BLINDNESS.

CAUSED BY DEFECT IN THE MITOCHONDRIAL FUSION GENE. THERE IS A SECOND DISEASE CALLED SHARKA TYPE II A CAUSED BY AGAIN HETEROZYGOUS MUTATIONS IN MFM2. SO MOST OR THERE ARE MANY FORMS OF CMT. THE MAJOR FORMS ARE DEMILEATING DISEASES. THEY ARE A DEFECT IN THE SWAN CELL. BUT IN TYPE II A, THIS IS AN EXKNOP THEE WHERE THE NEURON ITSELF IS DEFECTIVE. AND THING IS A QUITE INTERESTING DISEASE BECAUSE THIS EFFECTS MOTOR AND SENSORY NEURONSS WHOSE CELL BODIES ARE LOCATED NEAR THE SPINAL CORD BUT THEN INTERVENE THE EXTREMITIES.

SO IN THIS DISEASE, PATIENTS HAVE WEAK HANDS AND FEET AND ALSO SENSORY LOSS. AND SO IN THIS DISEASE WHERE THERE IS A DEFECT IN THE MITOCHONDRIAL FUSION GENE, IT’S ONLY THE LONGEST PERIPHERAL NEURONS THAT ARE EFFECTED AND THE MORE PROXIMAL NEURONS ARE SPARED. SO TO LOOK AT SOME OF THESE ISSUES ABOUT WHY MITOCHONDRIAL FUSION SEEMS TO BE PARTICULARLY IMPORTANT FOR NEURONS, WE HAVE BEEN STUDYING MOUSE THAT HAVE KNOCKOUTS IN MFM1 OR 2 AND MUTATIONS IN EITHER ONE OF THOSE GENES WILL LEAD TO EMBYRONIC LETHALLALITY BUT WE MADE.

CONDITIONAL KNOCKOUTS TO HELP US LOOK AT THE POST EMBYRONIC ROLES OF THESE GENES IN THE CASE OF MFM2 KNOCKOUTS, IF WE BY PASS THE PLACENTAL DEFECT, THOSE SPLICE A VERY SEVERE ATAXIA AND IT IS ASSOCIATESSED WITH A SAY BELLA DEFECT. SO THIS IS AN EXAMPLE HERE. SO IN WILDTYPE ANIMALS, THIS IS THE CEREBELLUM SEVEN DAYS AFTER BIRTH. IT LOOKS RELATIVELY NORMAL IN THE MFM2 MUTANT BUT THE CEREBELLUM IS UNDERDEVELOPED. BUT IF YOU LOOK AT ANIMALS THAT ARE JUST ONE WEEK LATER, IN WILDTYPE ANIMALS, THERE IS EXTENSIVE CELL MIGRATION AND.

DIFFERENTIATION THAT OCCURS IN THE CEREBELLUM AT THIS TIME. BUT IN AN MFM2 KNOCKOUT, THERE IS ATROPHY OF THIS PART OF THE BRAIN. AND IT TURNS OUT THAT THERE IS A SPECIFIC NEURON THAT IS DEFECTIVE. SO, THIS IS JUST A HISTOLOGICAL SLIDE WHERE YOU CAN CONSIDER THIS TO BE THE OUTSIDE OF THE CEREBELLUM AND THIS IS CALLED THE MOLECULAR LAYER AND THIS IS THE INTERNAL GRAN LEGAL LAYER. THE GRANUAL CELLS ARE THE MOST ABUNDANT CELLS IN THE CEREBELLUM. AT THE INNER FACE A CELL TYPE CALLED THE PREKINSY CELL.

THAT IS THE NEURON THAT IS DEFECTIVE IN THESE ANIMALS. SO IF WE LOOK USING A MARKER FOR PURCINCHY CELLS, THIS IS HOW THEY DEVELOP IN THE 50 TWO WEEKS OF LIFE. SO SIX DAYS AFTER BIRTH THERE IS A LAYER OF THESE CELLS HERE IN THIS PART OF THE CEREBELLUM. AND OVER TIME, THESE CELLS WILL EXTEND OUT THEIR DENDRITIC PROCESSES INTO THE MOLECULAR LAYER SO THAT BY DAY 15, YOU CAN SEE HOW EXTENSIVE THAT DENDRITIC LAYER IS. BUT IN ANIMALS THAT LACK MFM2, THEY START OFF WITH LAYER OF.

THESE CELLS BUT BY 10 DAYS AFTER BIRTH, YOU CAN SEE THERE IS A PRETTY SEVERE DEFECT. SO THEY HAVE THESE CELLS BUT THEY ARE DENDRITES THAT ARE MUCH SHORTER AND THEY HAVE THE REDUCED DENDRITIC SPINES. AND THESE CELLS WILL DIE OVER THE NEXT WEEK SO AT TWO WEEKS AFTER BIRTH, THERE IS VERY FEW PURKINJE CELLS IN THE CEREBELLUM AND THIS LEADS TO ATAXIA. SO IN STUDYING WHAT THE DEFECTS ARE IN THESE CELLS THAT LACK MITOCHONDRIAL FUSION, IT TURNS OUT THEY HAVE A VERY SEVERE RESPIRATORY DEFECT. AND THE BASIS FOR THAT IN PART,.

IS THAT THEY HAVE A DEFECT IN MAINTENANCE OF MITOCHONDRIAL DNA. SO, HERE WE ARE RETURNING BACK AGAIN TO FIBROBLASTS AND IN FIBROBLASTS WILDTYPE CELLS, THE GREEN HERE SHOWS THE MITOCHONDRIA AND THE RED IS A NUCLEAR STAIN. AND SO YOU CAN SEE THESE MITOCHONDRIA CONTAIN THESE COMPACT DNA CONTAINING STRUCTURES CALLED NUCLEASE. SO THESE ARE THE GENOMES OF THE MITOCHONDRIA. AND EVERY MITOCHONDRIAL TUBUAL HAS AT LEAST ONE EMPTY DNA NUKE LLOYD BECAUSE THE MITOCHONDRIAL GENOME ENCODES FOR ESSENTIAL COMPONENTS OF THE RESPIRATORY CHAIN. IN CELLS THAT LACK MITOCHONDRIAL FUSION, YOU CAN SEE THEY ARE.

FRAGMENTED. THEY DO RETAIN MITOCHONDRIAL DNA BUT YOU CAN SEE THAT A LARGE POPULATION OF THE MITOCHONDRIA LACK NIKE LLOYDS. THESE MITOCHONDRIA ARE RESPIRATORY DEFICIENT. AND SO OUR MODEL FOR WHAT THE FUNCTION OF MITOCHONDRIAL FUSION IS, IS THAT IT ALLOWS CONTENT EXCHANGE BETWEEN MITOCHONDRIA AND THIS CONTENT EXCHANGE IS IMPORTANT TO MAINTAIN THE FUNCTION OF THE MITOCHONDRIAL POPULATION. SO WE THINK THAT IN WILDTYPE CELLS, THERE IS A POPULATION OF MITOCHONDRIA THAT CONTINUOUSLY INTERACTS AND EXCHANGES CONTENT WITH EACH OTHER. AND YOU CAN IMAGINE THAT YOU CAN HAVE INDIVIDUAL MITOCHONDRIA.

THAT SPORADDICALLY DEVELOP A DEFECT. AND THERE COULD BE MANY REASONS FOR THIS. ONE REASON WOULD BE THAT THERE IS A DIVISION EVENT IN WHICH A MIGHT DONDRIA FAILS TO INHERIT A MITOCHONDRIAL DNA NUKE LLOYD. BUT THOSE DEFECTS CAN BE REPAIRED BECAUSE THAT MITOCHONDRIA CAN BE CONFUSED WITH A NEIGHBORING MITOCHONDRIA AND THEN OF SUBSEQUENT FUSION EVENT LEADS TO COMPUTATION OF THAT DEFECT. AND IN CELLS THAT LACK MITOCHONDRIAL FUSION, ONCE THESE DEFECTS OCCUR, THEY REMAIN OR PROLONGED OR PERMANENT. SO IN OUR SYSTEM WHERE WE LOOK AT THE DEFECTS THAT ARISE DUE TO.

A DEFECT OF MITOCHONDRIAL FUSION, WE ALSO SEE THE PROTECTIVE EFFECTS OF MITOCHONDRIAL FUSION. THERE IS ALSO A COMPLEMENTARY VIEW THAT WHEN DEFECTS ARE VERY SEVERE, IT MIGHT BE BENEFICIAL TO RESTRICT THE FUSION OF THOSE MITOCHONDRIA SO THEY CAN BE SEGGREATED AND DEGRADED BY AUTOPHAGY. SO FOR EXAMPLE, WE HAVE SHOWN WHEN MITOCHONDRIA LOSE COMPLETELY LOSE MEMBRANE POTENTIAL, THEY NO LONGER CAN FUSE WITH NEIGHBORING MITOCHONDRIA AND THOSE THEN BECOME SEGREGATED AND PERHAPS ARE DEGRADED BY AUTOPHAGY. SO IT CAN BE THAT DEPENDING ON THE SEVERITY OF MITOCHONDRIAL DYSFUNCTION, EITHER THOSE.

MITOCHONDRIA CAN BE REPAIRED BY CONTENT MIXING OR PERHAPS THEY ARE SEGREGATED WHEN THE DEFECT IS TOO SEVERE AND THEN DEGRADED. SO IN THE NEXT PART OF MY TALK, I WOULD LIKE TO SUMMARIZE SOME OF OUR STUDIES ON THE FUNCTION OF MITOCHONDRIAL FUSION IN SKELETAL MUSCLE. SO WE WERE INTERESTED IN SKELETAL MUSCLE BECAUSE OBVIOUSLY, MITOCHONDRIAL ARE VERY IMPORTANT IN THAT CELL TYPE. AND DEPENDING ON THE TYPE OF SKELETAL MUSCLE, FOR EXAMPLE, WHETHER IT IS OXIDATIVE OR THE MITOCHONDRIA HAVE DIFFERENT DEGREES OF ABUNDANCE BUT IN GENERAL, THEY ARE.

HIGHLY THEY ARE POSITIONED VERY PRECISELY IN THE CELL. SO, HERE YOU CAN SEE FOR EXAMPLE, THAT THERE ARE PAIRS OF MITOCHONDRIA THAT ARE POSITIONED ON THE TWO SIDES OF THE Z DISK IN THIS. SO BECAUSE THE MITOCHONDRIA AND SKELETAL MUSCLE ARE SO PRECISELY POSITIONED IN CONTRAST TO THE CASE OF FIBROBLASTS WHERE YOU CAN SEE THEM MOVE AROUND THE CELL CONTINUOUSLY, WE THOUGHT IT WOULD BE GOOD TO ASK WHETHER MITOCHONDRIAL FUSION IS IMPORTANT IN THIS CELL TYPE. SO WE KNOCKED OUT MITOFUSE INS IN SKELETAL MUSCLE USING THE MLC.

CRE DRIVER SYSTEM DEVELOPED BY SEVERE BURGEN. WHAT WE FOUND IS THAT THESE MICE HAVE SEVERE DEFECTS. SO THIS IS A MUSCLE SPECIFIC OF BOTH MITOFUSE INS. THEY HAVE LOW BODY WEIGHT, BLOOD TEMP AND GLUCOSE HIGH SERUM LACTATE THAT GETS WORSE WITH EXERCISE. THEY HAVE CHARACTERISTICS THAT ARE SUGGESTIVE OF A DEFECT. WHEN YOU LOOK AT THE MUSCLES FROM THESE ANIMALS, THE MUSCLES ARE DEEPER RED, WHICH MIGHT IS THAT THE THERE IS MORE OR HIGHER LEVEL OF MITOCHONDRIAL BINDING. AND THAT TURNS OUT TO BE THE CASE IN WHICH I WILL SHOW YOU IN.

A SECOND. SO WE DID SOME HISTOLOGICAL STUDIES OF THE MUSSEL FROM THESE ANIMALS. SO IN WILDTYPE MUSCLES, USING STAINING FOR COMPLEX TWO AND COMPLEX 4, WHERE THE COMPLEX 4 STAINING IS BROWN STAIN, YOU CAN SEE IN THE WILDTYPE ANIMALS, TRANSVERSE SECTIONS OF THE MUSCLE FIRST SHOW A HOMOGENEOUS STAIN MUSCLE SECTION THAT OVER THE FIRST TWO MONTHS OF LIFE DIFFERENTIATES INTO THIS CHECKER BOARD APPEARANCE. SO HERE IS A MUSCLE FIBER THAT HAS HIGH MITOCHONDRIAL FUNCTION AND HERE IS A MUSCLE FIBER THAT HAS LOW MITOCHONDRIAL FUNCTION. BUT WHEN WE LOOK AT ANIMALS THAT.

LACK THE MITOFUSE INS IN SKELETAL MUSCLE, WE SEE THAT THEY HAVE SMALLER DIAMETERS FOR THEIR MUSCLE FIBERS AND THEY HAVE THIS INTENSE BLUE STAIN, WHICH IS AN INCREASE IN COMPLEX 2. SO IN THIS TYPE OF STAINING, INCREASE IF COMPLEX 2 OFTEN INDICATES A MITOCHONDRIAL DYSFUNCTION BECAUSE OF THE DEFECT IN HEIGHT CONNED REAL DNA. I’LL EXPLAIN THAT IN A SECOND. BUT THESE ANIMALS DEVELOP RESPIRATORY DEFICIENCY IN THE MUSCLE FIBERS. SO WE COLLABORATED WITH MIKE McCAVEAT JOHN’S HOPKINS TO DO ON THESE MUSCLES. WE FIND IN SKELETAL MUSCLES, WE.

HAVE A CLASSIC NANCY WILDTYPE CELLS WHERE THERE ARE PAIRS OF MITOCHONDRIA AS I MENTIONED THAT FLANK THE Z DISK. BUT IN CONTRAST, IN ANIMALS THAT LACK MIGHT FUSE INS, YOU HAVE THIS OVER ABUNDANCE OF MITOCHONDRIA AND THEY PROLIFERATE AND FILL THE SPACE BETWEEN MYOFIBRILS AND IN ADDITION, WHEN YOU LOOK AT THE RESULT STRUCTURE OF THESE MITOCHONDRIA, YOU CAN SEE THEY ARE SMALLER AND THEY LACK THE INTERNAL STRUCKER R.URE THAT THE WILDTYPE HAVE STRUCTURE. SO THERE IS A DEFECT IN THE STRUCTURE AND ABUNDANCE OF THE INTRAFIBULAR MITOCHONDRIA IN.

THESE SKELETAL MUSCLE CELLS. THIS IS ANOTHER PLACE IN SKELETAL MUSCLE WHERE MITOCHONDRIA ARE ABUNDANT THAT’S UNDER THE PLASMA MEMBRANE. SO THESE ARE THE SUBSARCOLEMALAL MIGHT QUANDARY MITOCHONDRIA. IN MUSCLE THAT LACKS MITOFUSE INS, THERE IS A PROLIFERATION AND AGAIN THEY HAVE HETEROGENERATEY AND SWELLING AND ALSO A LOSS OF INTERNAL STRUCTURE. THERE IS A DEFECT IN THE ELECTRON TRANSPORT CHAIN AND MITOCHONDRIAL PROLIFERATION. SO THESE KINDS OF PROBLEMS ACTUALLY RESEMBLE THE PROBLEMS THAT YOU SEE IN THE HUMAN DISEASES THAT ARE CAUSED BY DEFECTS IN MITOCHONDRIAL DNA. SO THERE IS A CLASSIC HUMAN.

DISEASES CALLED IN SELF LOW MYOPATHIES, MATERNALLY INHERITED AND DUE TO MATERNALLY INHERITED MUTATIONS IN THE MITOCHONDRIAL GENOME. SO THIS IS THE CIRCULAR MITOCHONDRIAL GENOME, 16 KILOBASES IN LENGTH. AND THESE ARE THE LOCATIONS EVER VARIOUS MUTATIONS THAT GIVE RISE TO CLINICAL SYNDROMES. SO WE WANTED TO ASK IN THIS SKELETAL MUSCLE VISITS WE DON’T HAVE MITOFUSINS AND HAVE THE MITOCHONDRIAL DEFECT THAT RESEMBLES EN SEF LA MAYOPATHYS, IS THERE A DEFECT IN THE GENOME. SO WE LOOKED TO THE LEVELS OF MTDNA IN THE MITOCHONDRIA. IF WE LOOK AT WILDTYPE ANIMALS,.

THIS IS THE LEVEL OF MITOCHONDRIAL DNA COMPARED TO NUCLEAR DNA. THIS DEFECT IS DEPENDENT ON LOSING BOTH MITOFUSE INS. SO IF YOU LEWIS JUST MFN1 OR 2, THAT DOESN’T OCCUR. THERE IS A PROLIFERATION EVER MTDNA DURING THE FIRST FEW MONTHS OF LIFE. IF YOU TRACK THE LEVELS OF MTDNA DURING DEVELOPMENT, WHAT WE FIND IN WILDTYPE ANIMALS IS THAT THE LEVELS INCREASED GREATLY IN THE FIRST TWO MONTHS OF LIFE. AND THIS IS ASSOCIATED WITH THE DIFFERENTIATION OF THE MUSCLE FIBERS AS I SHOWED YOU IN THE PREVIOUS SLIDES.

BUT IN ANIMALS THAT LACK MFM1 AND 2, THEY HAVE REDUCED LEVELS AS EARLY AS ONE WEEK OF AGE AND THAT LEVEL DOESN’T INCREASE AS YOU SEE IN THE WILDTYPE ANIMALS. SO, AT 7 WEEKS OF AGE, YOU HAVE A VERY SEVERE DEFECT. SO LET ME SUMMARIZE THIS PART OF THE TALK. SO, WE WERE WE ASKED WHETHER MITOCHONDRIAL DIE NAM 6 IMPORTANT FOR MTDNA STABILITY AND WE FOUND THAT IN THE CASE OF SKELETAL MUSCLE, IT’S IMPORTANT FOR MAINTENANCE OF MTDNA LEVELS AND I DIDN’T SHOW YOU THIS BUT.

THERE IS A DEFECT IN THE FIDELITY OF MTDNA. SO IN THE ABSENCE OF MITOFUSINS, THERE IS INCREASE IN POINT MUTATIONS AND DELETIONS. SO WE THINK THAT MITOCHONDRIAL FUSION PROBABLY PLAYS A PROTECTIVE ROLE IN THE PATH APOLOGIES THAT INVOLVED MTDNA. THIS IS ALSO AN ASSOCIATION WITH MITOCHONDRIAL FUSION AND THE ABILITY TO TOLERATE MTDNA MUTATIONS BUT I’M NOT SHOWING THE DATA FOR THAT TODAY. SO, WHAT THESE TYPES OF STUDIES AND ALSO HUMAN GENETIC STUDIES HAVE SHOWN, IS MITOCHONDRIAL FUSION FISSION ARE IMPORTANT FOR A WIDE RANGE OF TISSUES IN.

MAMMALS. SO FOR EXAMPLE, FOR MITOCHONDRIAL FUSION, FROM THE HUMAN DISEASES, WE KNOW THAT OPA1 IS IMPORTANT IN THE RETINOGANGLYIA CELLS IN THE EYE. MFN2 IS IMPORTANT IN THE NERVES. MFN2 IS IMPORTANT IN THE CEREBELLUM AND BOTH MITOFUSINS ARE IMPORTANT IN SKELETAL MUSCLE. ALSO WORK FROM OTHER LABS SO FROM SHOWING THAT MICE THAT LACK MITOCHONDRIAL FISSION ALSO HAVE NEURONAL DEGENERATION AND THERE IS ALSO ONE HUMAN CASE IN WHICH A DEFECT IN MITOCHONDRIAL FISSION RESULTS IN PERINAILS LETHALITY. A LOT OF EVIDENCE PERINATAL LETHALITY. IMPORTANT IN CELLS NIPS MAMMALS.

SO, BECAUSE OF THIS, WE DECIDED IT WOULD BE IMPORTANT TO BE ABLE TO BETTER STUDY MITOCHONDRIAL DYNAMICS IN TISSUES. SO, MOST STUDIES OF MITOCHONDRIAL DYNAMICS RELY ON CULTURE CELL LINES BECAUSE IT’S EASIER TO GET IMAGED MITOCHONDRIAL DYNAMICS AT HIGH RESOLUTION IN THOSE CASES. BUT MOUSE KNOCKOUT STUDIES AND ALSO HUMAN GENETIC STUDIES INDICATE THAT MITOCHONDRIAL DYNAMICS IS IMPORTANT TISSUES SO WE CONTINUING IS IMPORTANT TO DEVELOP SYSTEMS TO MONITOR MITOCHONDRIAL DYNAMICS IN INTACT TISSUES. AND SO THE WAY THAT WE DID THIS IS TO TRY TO DEVELOP SOME MOUSE.

MODELS WHERE WE CAN IMAGE MITOCHONDRIA MORE EFFECTIVELY. AND SO THIS WAS WORK THAT WAS DONE BY ANNE FAMILIAR WHO WAS AN MDPh.D. STUDENT IN MY LAB. AND SO WHAT SHE DID WAS TO DEVELOPE OR TARGET A FLORA FOR TWO MITOCHONDRIA THAT IS PHOTO ACTIVATABLE. WE TARGETED THE TEND DRA TWO TO THE MITOCHONDRIA AND WE KNOCKED IN THIS CONSTRUCT INTO THE UBIQUITOUSLY EXEXPRESSED ROSA 26 LOCUS AND WE MADE TWO VERSIONS OF THIS MOUSE. IN ONE VERSION, THIS CONSTRUCT IS UBIQUITOUSLY EXPRESSED AND IN THIS MOUSE, ESSENTIALLY ALL THE.

CELLS IN THE BODY CONTAIN FLUORESCENTLYLABELED MITOCHONDRIA. IN THE SECOND VERSION, THE CONSTRUCT HAS A STOP SEQUENCE IN FRONT OF IT THAT IS FLANKED BY SITES, IN ORDER FOR THIS CONSTRUCT TO BE ACTIVE, YOU HAVE TO ADD CRE RECOMBINASE. SO WE CAN CONDITIONALLY ACTIVATE THIS MITOCHONDRIAL FLOR FORA SELECT ITCHILY AT DEVELOPMENTAL STAGES OR DIFFERENT TISSUES. FLUOROPHORE. ONE OF THE FEATURES IS IT IS CONVERTIBLE. IT’S NORMALLY GREEN BUT IF YOU ACTIVATE IT USING A LASER, YOU CAN TURN IT TO RED. AND THIS SYSTEM WORKS PRETTY WELL. SO HERE WE HAVE THE CONDITIONAL.

SYSTEM THAT I MENTIONED. SO WHEN WE ISOLATE FIBROBLASTS FROM THOSE MICE, THEY FIBROBLASTS DON’T HAVE FLORESCENT MITOCHONDRIA. BUT THEN WE CAN TRANSDUCE THOSE CELLS WITH A RETROVIRUS THAT CONTAINS CRE AND NOW THE MITOCHONDRIA IN THOSE CELLS ARE FLUORESCENTLY LABELED. SO HERE WE CAN SEE THE DIFFERENT MITOCHONDRIAL MOREOVERROLOGIES IN THE CELL SO THERE IS MITOCHONDRIA HERE AND A SHORT TUBIAL, LONG TUBIALS AND INTERCONNECTED TUBIALS. AND THEN WE CAN DO PHOTO ACTIVATION STUDIES TO LOOK AT THE FUSION EVER MITOCHONDRIA. SO HERE WHEN I UP THERE MOVIE, YOU WILL SEE PHOTO ACTIVATION.

SO HERE SEVERAL REGIONS OF MITOCHONDRIA ARE PHOTO ACTIVATED. WHEN YOU LOOK OVER HERE, THERE IS A FUSION EVENT THAT LEADS TO CONTENT MIXING AND THEY’LL BE ANOTHER EVENT HERE FOLLOWED BY A THIRD EVENT OVER HERE. SO THESE THIS MARKER IS LOCATED IN THE MATRIX OF THE MITOCHONDRIA. WHEN YOU GET CONTENT IT’S CHANGED AND THAT MEANS THERE ARE OUTER MEMBRANE AND INNER MEMBRANE FUSION THAT IS CURRENT. SO WHEN WE LOOK AT THE VARIOUS TISSUES, SO WHEN WE LOOK AT THE UBIQUITOUSLY EXPRESSED FORM OF THIS MOUSE, WE CAN FIND THAT.

THERE IS EXPRESSION OF THIS FLOR FORA IN MANY TISSUES. SO MANY TYPES OF NEURONS AND THE MYOCARD YUM, HEPATOCYTES IN KIDNEY CELLS. SO THESE ARE JUST FROZEN SECTIONS WHERE WE CAN QUICKLY GET A SENSE OF MITOCHONDRIAL MORPHOLOGY IN THE TISSUES AND ALSO LOOK IN LIVE CELLS. SOME OF THE LIVE CELLS THAT WE LOOKED AT ARE SPERM. SO THIS IS THE SPERM HEAD, THE TAIL, AND YOU CAN SEE THE PIECE OF THE SPERM THAT IS LIT IS WHERE THE MITOCHONDRIA DEN DRA IS AND WE CAN PHOTO ACTIVATE.

PART OF THAT. THIS IS FROM A LIGHT SKELETAL MUSCLE FIBER. AND AGAIN HERE ARE THE PAIRS OF MITOCHONDRIA, THE Z DISK IS RIGHT HERE AND THEN WE CAN ALSO ICE LATE THESE AND SEE THE MITOCHONDRIA ARE FLORESCENT. SO BY USING THE SYSTEM, WE CAN LOOK AT MITOCHONDRIAL DYNAMICS. SO HERE IS AN EXAMPLE. THIS IS SKELETAL MUSCLE. AND SO WE CAN PHOTO ACTIVATE A SUBSET OF MITOCHONDRIA AND THEN IF WE TRACK THE FLUORESCENCE IN A MOVIE, YOU CAN SEE THAT THERE CAN BE SO IN THIS THIS IS.

A LONGITUDINAL SECTION OF THE MUSCLE FIBER. SO IT IS RUNNING IN THIS DIRECTION. YOU CAN SEE THAT THERE ARE FUSION EVENTS THAT CAN OCCUR IN THIS DIRECTION AS WELL AS IN THIS DIRECTION. SO WE CAN USE THIS TO STUDY MITOCHONDRIAL DYNAMICS AND SKELETAL MUSCLE. WE CAN ALSO USE THIS SYSTEM TO BETTER UNDERSTAND THE CHANGES IN MITOCHONDRIAL SHAPE THAT OCCUR IN MOUSE KNOCKOUTS. SO REMEMBER I TOLD YOU EARLIER THAT IF WE KNOCKOUT MFN2 WE GET A DEFECT IN PRO KINSY CELLS. AN EXAMPLE OF THAT IS SHOWN HERE.

IF WE KNOCKOUT MFN2 IN ADULT PURKINJE CELLS, WE CAN ALLOW THE CELLS TO DEVELOP. SO THIS IS A STAIN WHERE THIS IS THE CELL BODY OF THE PURKINJE CELL AND THESE ARE THE DENDRITES. AT THREE MONTHS OF AGE, YOU CAN SEE THAT MOST OF THE PURKINJE CELLS ARE GONE. SO LOOK AT THIS SYSTEM USING THIS MITODEN DRA MOUSE. AND YOU CAN SEE THAT IN WILDTYPE SECTIONS, SO HERE ARE THE PURKINJE CELLS. THESE ARE THE MITOCHONDRIA, AND WHEN WE KNOCKOUT MFN2, YOU CAN SEE THAT THERE IS MUCH MORE.

SPARSE MITOCHONDRIA. AND THAT IS PARTICULARLY EVIDENT IN THE DENDRITIC PROCESSES. AND IN THIS OR THESE SLIDES HERE, WE ARE GETTING FROZEN SECTIONS TO GET A QUICK SINCE OF THE MITOCHONDRIAL MORPHOLOGY. BUT WE CAN GET MUCH HIGHER RESOLUTION IF WE USE ORGANIC SLICES. SO THERE IS A TECHNIQUE WHERE WE SIMPLY TAKE A SLICE OF THE BRAIN AND THEN CULTURE THOSE SLICES INTO CULTURE AND THIS ALLOWS THESE SLICES TO SURVIVE FOR SEVERAL MONTHS AND IT PRESERVES THE CONNECTIONS BETWEEN SOME OF THE NEURONS SO WE CAN VISUALIZE MITOCHONDRIAL DYNAMICS USING.

CONFOCAL MY COSCOPEY AND WE CAN ALSO MAKE PERTY BATIONS. AND WHEN WE DO THAT, WE GET BETTER IMAGE OF THE CELLS THIS SILENT CELL BODY AND THE DENDRITIC THIS IS THE CELL BODY AND THIS IS THE STAINING. YOU CAN SEE HOW DENSELY PACKED THE MITOCHONDRIA ARE IN THESE PROCESSES. IN A DIFFERENT PART OF THE ORGANIC SLICE, WE CAN SEE NEURONS IN THE MID BRAIN AND THESE ARE DOPAMINERGIC NEURONS PRESENT AND AGAIN WE CAN VISUALIZE THE MITOCHONDRIA IN THE CELLS. SO, WE CAN USE THIS SYSTEM TO.

LOOK AT DIFFERENT TYPES OF NEURONS IN THE BRAIN. SO IN THE LAST PART OF MY TALK, I WILL TALK ABOUT USING THE SYSTEM TO LOOK AT WHAT HAPPENS TO DOPAMINERGIC NEURONS WHEN THEY USE MFN2. SO, AS I’M SURE YOU ALL KNOW, SINCE RICHARD IS HERE, PARKINSON’S DISEASE HAS AN ASSOCIATION WITH MITOCHONDRIAL FUNCTION. SO PARKINSON’S DISEASE IS THE SECOND MOST COMMON NEURODEGENERATIVE DISEASE. IT’S A MOVEMENT DEFECT. AND FOR DECADES THERE HAS BEEN A LINK BETWEEN MITOCHONDRIAL FUNCTION IN PARKINSON’S DISEASE. AND THIS IS BECAUSE MITOCHONDRIAL TOXINS LIKE MPTP.

CAN CAUSE PARK INSONIAN SYMPTOMS IN MAMMALS AND IN HUMANS. MORE RECENTLY MORE DIRECT EVIDENCE THAT MITOCHONDRIAL FUNCTIONS IS INVOLVED IN PARKINSON’S DISEASE BECAUSE 10 OF PARKINSON’S DISEASE IS FAMILIAL AND THERE IS A NUMBER OF GENE THAT IS HAVE BEEN IDENTIFIED TO BE LINKED TO PARKINSON’S DISEASE AND TWO OF THEM ARE PARK IN AND PINK 1. THESE TWO GENES WORK IN A COMMON PATHWAY TO PRESERVE MITOCHONDRIAL FUNCTION. AND RICHARD HAS SHOWN THAT PINK ONE AND PAR IN ARE INVOLVED IN THE ELIMINATION OF THIS FUNGAL MITOCHONDRIAL. SO WHEN THEY BECOME.

DYSFUNCTIONAL, IT’S BEEN SHOWN THAT PARKIN LOCATES TO THOSE MITOCHONDRIA AND THAT SYSTEM CAN RESULT IN THE DEGRADATION OF THOSE DYSFUNCTIONAL MITOCHONDRIA. AND SO WE DID ONE STUDY WHERE WE LOOKED AT SOME OF THE CHANGE THAT IS OCCURRED IN THIS TYPE OF DEGRADATION. SO, WHEN MITOCHONDRIA BECOME DYSFUNCTIONAL IN THIS SYSTEM, PARKIN IS RECUTED ON TO THOSE DYSFUNCTIONAL MITOCHONDRIA AND IT IS A B3 UBIQUITIN LIGASE LEADING TO UBIQUITINATION ON THE MEMBRANES ON THE MITT CONNED REAL MEMBRANE AND LEADS TO THE UBIQUITIN PROTOSTOME SYSTEM CAUSING DEGRADATION ON MANY PROTEINS ON THE OUTER MEMBRANE.

AND THAT EVENT IS NECESSARY FOR THE DEGRADATION OF THOSE DYSFUNCTIONAL MITOCHONDRIA BY AUTOPHAGY. SO, IN PARKINSON’S DISEASE, THERE ARE GENES ASSOCIATESSED WITH THE DISEASE THAT SEEM TO EFFECT MITOCHONDRIAL DYNAMICS. AND IN ADDITION, IT’S ALSO BEEN SHOWN IN SOME ELEGANT FLY STUDIES THAT IF YOU PERTURB MITOCHONDRIAL DYNAMICS, YOU CAN PERTURB THE PHENOTYPE OF A PINK 1 OR PARKINKNOCKOUT. SO THERE HAS BEEN A NUMBER OF FLY LAB THAT IS HAVE SHOWN THIS ON HIGHLIGHTING WORK FROM THE LAB. SO HERE WE HAVE IN FLIES, A PINK 1 KNOCKOUT. IT LEADS TO APOPTOSIS IN THESE.

CELLS. BUT IF YOU THEN KNOCK DOWN THE FLY MITOFUSE IN, YOU CAN SUPPRESS THAT DEFECT OR IF YOU OVER EXPRESS DRP1, YOU CAN ALSO SUPRESS THAT. YOU CAN MODIFY BY MANIPULATING MITOCHONDRIAL DYNAMICS. SO JUST TO SUMMARIZE THE ARGUMENT. THERE ARE PARKINSON’S DISEASE ASSOCIATED MUTATIONS IN GENES THAT HAVE A LINK TO MITOCHONDRIAL DYNAMICS. SO FOR EXAMPLE, CELLS THAT LACK PINK 1 OR PARKIN CAN HAVE MITOCHONDRIAL MORPHOLOGY DEFECTS. IN ADDITION, THE EFFECT OF PARKINSON’S ASSOCIATED MUTATIONS CAN BE GREATLY MODULATED BY MITOCHONDRIAL DYNAMICS SO INCREASE FUSION OR INCREASED FISSION TO MODIFY DOSE EFFECTS.

SO BECAUSE OF THAT, WE DECIDED TO ASK WHAT IS THE ROLE OF MITOCHONDRIAL DYNAMICS IN DOPAMINERGIC NEURONS AND PARTICULARLY IN THE NIAGRA BECAUSE THAT’S RELEVANT TO PARKINSONS DISEASE SO THE WAY THAT WE DID THIS WAS TO AGAIN USE OUR CONDITIONAL MFN2 KNOCKOUT ANIMALS AND TO USE A MATING SCHEME WHERE WE USED THE DOPAMINE TRANSPORTER TO KNOCKOUT MFN1 OR 2 IN THE DOPAMINERGIC NEURONS AND INCORPORATED THIS MOUSE THAT ALLOWS US TO TRACK THE MIGHT CONNED REEL RIA. AND WHAT WE FOUND IS THAT IF WE KNOCKOUT THE MFN1, WE DON’T GET.

ANY PHENOTYPE AT ALL. BUT IF WE KNOCKOUT 2, WE GET ANIMALS THAT ARE RUNTED. SO THIS IS SHOWN HERE. SO HERE IS THE TRACE FOR WILDTYPE ANIMALS. JUST THE WEIGHT GAIN OVER TIME. AND YOU CAN SEE THAT IF THE ANIMALS LACK MFN2, THERE IS A PRETTY SEVERE DECREASE IN WEIGHT GAIN. AND IT TURNS OUT THAT THERE IS A PRETTY SEVERE MOVEMENT DEFECT IN THESE ANIMALS. I SHOULD POINT OUT THAT THESE ANIMALS, IF YOU JUST KEEP THEM IN NORMAL CAGES, THEY’LL DIE AT SIX WEEKS OF AGE DUE TO LACK OF.

FEEDING. BUT IF YOU PUT FOOD AND WATER AT THE BOTTOM OF THE CAGE, THEY’LL LIVE FOR OVER A YEAR. SO THAT ALLOWS US TO LOOK AT THE LONGTERM PHENOTYPES OF THESE MICE. AND THIS IS AN OPEN FIELD TEST WHERE A MOUSE IS PLACED INTO AN OPEN FIELD AND THEN YOU SIMPLY TRACK THE MOVEMENTS IN THAT SPACE. AND SO THESE LINES INDICATE THE MOVEMENT OF THE MICE AND YOU CAN SEE THAT MFN2 DEFICIENT ANIMALS HAVE A MOVEMENT DEFECT THAT IS DETECTABLE AS EARLY AS FOUR WEEKS OF AGE AND PROGRESSIVELY.

GETS WORSE. AND FOR EXAMPLE, IF YOU SIMPLY CALCULATE OR MEASURE THE DISTANCE TRAVELED, THE DISTANCE THAT THESE MUTANT ANIMALS TRAVEL IS REDUCED AT FOUR WEEKS OF AGE AND IT SEEMS TO PLATEAU OUT AT EIGHT11 WEEK OF AGE. AND THERE ARE SIMILAR RESULTS WHEN WE LOOK AT HOW FAST THESE ANIMALS MOVE. ALSO THEIR REARING AND THE TIME THEY STAY IMMOBILE. SO OBVIOUSLY BECAUSE WE ARE KNOCKING OUT MFN2 IN THE DOPAMINERGIC SYSTEM, WE WANT TO LOOK AT THE CONSEQUENCES FOR THE NEURONS IN THIS SYSTEM. SO THE FIRST THING THAT WE.

LOOKED AT WAS TO LOOK AT THE DISTAL PROJECTIONS OF THESE NEURONS. SO THE THERE ARE DOPAMINERGIC NEURONS IN THE SUBSTANTIAL NIAGRA AND THEY PROJECT TO THE STRIATUM AND SO WE CAN LOOK AT THOSE TERMINALS AT THE STRIATUM BY STAINING FOR TYROSINE HYDROXYLASE. SO THIS IS THE STRIATUM OVER HERE. AND WE’RE SIMPLY STAINING FOR TH AND THAT TELLS US THE ABUNDANCE OF THE TERMINAL AT THE STRIATUM. AND WHAT YOU CAN SEE IS THAT EARLY AS THREE WEEKS OF AGE, THERE IS REDUCED STAINING IN THE STRIATUM SUGGESTING THAT THERE.

IS A DEFECT IN THE NERVE TERMINALS IN THIS PART OF THE DOPAMINERGIC SYSTEM AND WHEN YOU GO OUT TO 11 WEEKS, THE STAINING IS ALMOST ALL GONE. AND THIS CAN BE QUANTIFIED. THEN IF WE WORK BACKWARDS IN THE CIRCUIT ASK WE LOOK AT THE CELL BODIES WE FIND THAT AT THREE WEEKS OF AGE WHEN WE LOOK AT THE SUBSTANTIAL NIAGRA, AND WE LOOK FOR HT STAINING, THE CELLS BODIES ARE PRESENT. SO THERE IS A DISTAL DEFECT IN NEURONS. WITH WE LOOK AT THE CELL BODIES THEY ARE NORMAL BUT AT 11 WEEKS.

THERE IS DAY DEFECT AT 14 WEEKS. SO, THIS IS A QUANTIFICATION OF THAT RESULT. SO IN CONTRAST TOKING AT THE NERVE TERMINALS, WHEN WE LOCK AT CELL BODIES, AT THREE WEEKS THEY ARE NORMAL AND 89 WEEKS DURING NORMAL, AND ONLY AT 11 AT 1012 WEEKS TO SEE THIS DEFECT IN THE CELL BODIES. SO WHAT HE WE THINKSHIPS A RETRO GRADE DEFECT AT THE NERVE TERMINAL AND THEN CELL DEGENERATION. AND THIS, AS NOTICED, BECAUSE IT DEALS WITH MFN2, HAPPENS TO INVOLVE A MITOCHONDRIAL DEFECT. SO USING THE ORGANELLE SLICED.

CULTURES THAT I MENTIONED IN CONJUNCTION WITH THE MITODEN DRA, YOU CAN SEE THAT WHETHER YOU LOOK AT PROXIMAL PROCESSES OR DISTAL PROCESSES OF THOSE DEEPA MA NERGIC NEURONS. THE KNOCKOUT SPLICE GREATLY REDUCED NUMBERS OF MITOCHONDRIAL. AND THERE IS ALSO A PRETTY SEVERE DEFECT IN THE TRANSPORT OF MITOCHONDRIA IN THESE NEURONS. SO HERE IS A CONTROL NEURON WHERE WE ARE LOOKING AT A DENDRITE AND ONE OF THESE DOPAMINERGIC NEURONS AND THE SLICE CULTURE AND HERE WE EFFECTO ACTIVATE A CLUSTER OF MIGHT MITOCHONDRIA AND THEN TRACK THESE OVER TIME AND SO.

THIS IS A GRAPH WHERE TIME IS IN THIS DIRECTION AND SO THESE VERTICAL THESE DO IAGONAL LINES OVER HERE INDICATE MOVEMENT OF MITOCHONDRIA FROM THIS CLUSTER AS THEY TRAVEL ALONG THIS PROCESS. AND IN CONTRAST, WHEN WE LOOK AT MFN2 KNOCKOUT NEURONS, HERE WE PHOTO ACTIVATE A CLUSTER OF MITOCHONDRIA. YOU CAN SEE THERE ARE VERY FEW TRANSPORT EVENTS THAT COME OUT OF THIS CLUSTER. SO WE CAN QUANTIFY THIS AND FROM IS DEFECT IN BOTH THE NUMBER OF TRANSPORT EVENTS AS WELL AS THE VELOCITY OF THESE EVENTS.

SO WE THINK THAT WOO TRANSPORT DEFECT IN MICE WHICH LEADS TO THIS RETRO GRADE DEFECT IN THE NEURONS. SO TO SUMMARIZE THIS LAST PART OF THE TALK, SO WE HAVE BEEN DEVELOPING MOUSE MODELS TO STUDY MITOCHONDRIAL DYNAMICS AND USED IT TO STUDY DYNAMICS IN DOPAMINERGIC NEURONS. READING SO WE THINK THAT THIS MOUSE MODEL MIGHT BE A GOOD MODEL TO LOOK AT THE CELL BIOLOGICAL DEFECTS THAT OCCUR IN THIS TYPE OF DEGENERATION. SO LET ME THANK THE PEOPLE WHO DID THIS WORK. SO, THE WORK WITH THE MOUSE.

MODEL TO LOOK AT MITOCHONDRIAL DYNAMICS, AND DOPAMINERGIC NEURONS IS ANH PHAM AND LOOKING AT SKELETAL MUSCLE AND CEREBELLUM DEFECTS IS DONE BY HSIUCHEN CHEN, A SENIOR SCIENTIST IN THE LAB. THE WORK I MENTIONED ON DEGRADATION EVER MITOCHONDRIA OUTER MEMBRANE PROTEINS IN AUTOPHAGY IS DONE BY NICKIE CHAN AND SOME OF THE WORK ON THE DOPAMINERGIC NEURONS WAS DONE WITH HELP FROM ANDREW STEELE A RESEARCH FELLOW AT CAL TECH AND WORK HAS BEEN DONE FROM THE LONG TERM COLLABORATION WITH MICHAEL McCARY FROM JOHN’S HOPKINS. THANK YOU VERY MUCH.

APPLAUSE gtgt THE TRANSGENIC MOUSE AND THE REPORTER PROTEINS WHICH IS INTERESTING THAT THE PICTURE YOU SHOWED IN THE SKELETAL MUSCLE, WAS THAT IN VIVO OR A MUSCLE REMOVED FROM THE ANIMAL BECAUSE THAT WAS A HIGH RESOLUTION PICTURE. gtgt THAT IS A MUSCLE REMOVED. SO EITHER SO WE CAN DO IT BOTH WAYS. SON TO HAVE THE ENTIRE MUSCLE AND IMAGE IT AND THE OTHER WAY IS TO TEASE OUT MUSCLE FIBERS. AND IN BOTH CASES IT’S NOT IN THE IN TACT ANIMAL. gtgt IN THE MUSCLE, YOU SAW WHAT.

LOOKED LIKE SOME RED AND YELLOW AREAS CONSISTENT WITH FUSION. COULDN’T THAT BE THE FUSION FROM PARTIALLY ERATE A. RADIATED WHERE YOU HAVE SOME RED DYE AND GREEN DYE AND WHAT YOU’RE LOOKING AT IS THE FUSION LIKE IT SHOWED SOMETIME AGO gtgt SO WHEN WE PHOTO ACTIVATE, DEPENDING ON THE DEGREES, YOU CAN GET ALL DIFFERENT FUSES. SO FOR EXAMPLE, MITOCHONDRIAL IS PARTIALLY PHOTO ACTIVATED. BUT IF WE MAKE MOVIES, WE CAN SEE CONNECTIONS BETWEEN MITOCHONDRIA IN WHICH WE TRANSFER AND SEE THOSE STEPWISE TRANSFER ON TO ANOTHER MITOCHONDRIAL. gtgt FROM WHAT YOU SHOWED IT’S.

CLEAR IF YOU ALTER THE MITOCHONDRIAL FISSION AND FUSION MACHINERY THAT YOU CAN GET CHANGES IN THE MOREOVERROLOGY AND THE FUNCTION OF MITOCHONDRIA. BUT YOU ALSO SHOWED THAT CELL CULTURE PARTICULARLY THAT FISSION AND FUSION EVENTS ARE HELPING ON THE SECOND TIME SCALE WHERE AS IN THE SKELETAL MUSCLE MAY BE HAPPENING ON THE ORDER OF MINUTES OR MAYBE HOURS. SO WONDER FIGURE YOU HAD INSIGHTS INTO WHAT THE SIGNAL IS THAT TELLS THEM WHEN TO HAVE FISSION AND FUSION EVENTS gtgt RIGHT. I AGREE THAT THE MITOCHONDRIAL FUSION AND FISSION EVENTS ARE.

MUCH WE SEE MANY FOR IN CULTURE THAN IN SKELETAL MUSCLE. WE DON’T KNOW WHAT THE SIGNALS ARE AND THERE HAVE BEEN SOME INTERESTING FINDINGS. FOR EXAMPLE, MITOCHONDRIAL FISSION IS REGULATED BY CELL CYCLE. IT’S ALSO REGULATED BY NUTRIENT STATUS. AND THERE ARE OTHER TYPES CELLULAR STRESSES THAT REDUCE MITOCHONDRIAL FUSION BUT I WOULD SAY IN THE NORM CELLS, WE DON’T KNOW WHAT THEY ARE. gtgt DIDN’T IT BECOME CLEAR TO ME WHY THE PARKINSON’S MICE THERE DOPAMINERGIC NEURONS DIE. IS IT BECAUSE YOU HAVE REDUCTION IN THE NUMBER OF MITOCHONDRIA.

OR CONFOUNDED BY THE FACT THEY HAVE OR IS IT MITOCHONDRIAL DNA MUTATIONS gtgt I THINK THERE IS A CLEAR I DON’T THINK THERE IS A CLEAR ANSWER TO THAT. SO, EVEN IN SPORADIC PARKINSON’S DISEASE, THERE ARE SOME STUDIES THATIGED KATE THAT THEY HAVE REDUCTIONS. SO THE SIMPLE ANSWER IS THAT MAYBE THOSE NEURONS ARE MORE SENSITIVE TO REDUCED MITOCHONDRIAL RESPIRATION ACTIVITY. AND THERE ARE SOME ARGUMENTS WHY THOSE NEURONS MIGHT BE. SO FOR EXAMPLE, IT’S BEEN ARGUED THAT THOSE NEURONS ARE METABOLICALLY HIGHLY ACTIVE SO THAT IS ONE POSSIBLY.

Gtgt DO YOU SEE ANY CHANGING OPTIC NERVE DEGENERATION DO YOU FIND ANY OPTIC NERVE DEGENERATION IN MITOFUSION TO MICE AND ANY VISUAL BEHAVIOR DEFECTS IN PART II, MUTATION VISIT PROBLEMS WITHS FUSION. SO IF YOU HAVE THIS OTHER MEMBRANE FUSION DEFECTS, YOU MAY ALSO SEE SOME SORT OF OPTIC NEUROPATHY. DID YOU HAVE A LOOK AT BEHAVIOR WITH MARRYING THESE MICE AND MFN2 KNOCKOUTS gtgt YOU’RE ASKING IF THERE IS ANY OPTIC DEFECTS. gtgt NEUROPATHY OR VISUAL BEHAVIOR DEFECTS DID YOU EVER CHECK THAT gtgt SO WE HAVEN’T LOOKED AT OPTIC.

DEFECTS. SO WE DON’T KNOW. BUT I WOULD SAY THAT IN MY TALK, I MENTIONED THAT THERE IS ADDOOMED DOMINANT APATHY BETWEEN BLINDNESS AND THEN CM28. SO WHEN THIS WAS DISCOVERED, IT SEEMED LIKE THIS REALLY DISPARATE DISPARATE TWO SYSTEM TAC HAVE THE CLINICAL PHENOTYPES. AND THAT IS THE CASE. BUT AS PEOPLE IDENTIFIED MORE AND MORE FAMILIES, THEIR FAMILIES WHERE THERE IS OVERLAP. SO THERE ARE CMT PATIENTS THAT HAVE OPTIC ATROPHY AND AT THE SAME TIME THERE ARE PATIENTS WITH OPA1 MUTATION THAT IS ALSO HAVE PERIPHERAL NEUROPATHY.

SO THERE IS DEFINITELY OVERLAP BETWEEN THE TWO CLINICAL SYNDROMES. gtgt SO WHY DO YOU BELIEVE THAT THE OPA IS SPECIFIC TO THE EYE AND THE NERVES WHEN YOU SHOWED WHEN YOU DISRUPTED THE SKELETAL MUSCLE THERE IS A HUGE SKELETAL MUSCLE NERVE DEVELOPS. gtgt SCORE IN HUMAN DISEASES THERE IS A SUBTLE DEFECT. THESE ARE HETEROZYGOUS MUTATIONS. AND FOR EXAMPLE, WE DO HAVE SO WE HAVE KNOCKED IN A COUPLE OF THESE ALLELES INTO MICE AND THERE IS NO DEED DEFECT. SO IT’S A SUBTLE DEFECT. gtgt IN HUMANS IT’S EASIER TO.

DETECT ANY KIND OF PHENOTYPE AND IF YOU SEE ANY PROBLEMS, IT’S NOT THESE MICE CANNOT DO THAT. gtgt RIGHT. gtgt VERY NICELY CHANGES THAT OFFERED BETWEEN MITOCHONDRIAL DNA AND THE NUCLEUS DNA DO YOU HAVE A SIMILAR STUDY FOR BRAIN SLICES AT WHAT TIME DO THEY LEVEL gtgt WE HAVEN’T LOOKED AT MITOCHONDRIAL DNA CONTENT IN THE BRAIN. gtgt SO SOME OF THE REDUCTIONS HAVE BEEN SHOWN INDISCERNIBLE DO THEY EFFECT OTHER PROTEINS gtgt I DON’T THINK I MEAN, THOSE TOXINS ARE PRIMARILY INHIBITING COMPLEX ONE SO I.

DON’T THINK THAT THERE IS A DIRECT EFFECT ON THE MIGHT FUSE INS OR OPA1 IN THAT CASE. gtgt SO THIS CONCEPT APPLIES NICELY. SO WHAT HAPPENS WHEN CELL BECOMES MANAGEABLE INDISCERNIBLE YOU MEANING THE RELATIONSHIP OF DYNAMICS THERE IS REALLY NOT MUCH INFORMATION ON THAT. I THINK THERE IS ONE STUDY THAT FOUND THAT IN A TYPE OF LUNG CANCER THERE WAS MITOCHONDRIAL FISSION. AS FAR AS I KNOW THAT’S THE ONLY STUDY RELEVANT TO THAT. gtgt BUT YOU CAN PREDICT THAT WHEN FISSION AND FUSION SYSTEMS MESS.

UP IT WILL BE DIFFICULT INDISCERNIBLE gtgt YES. . LOW AUDIO gtgt I DIDN’T UNDERSTAND THE FIRST PART gtgt THERE ARE SOME PROTEINS WHICH ARE IMPLICATED WITH A MUTATION THAT LEAD TO ATAXIA INDISCERNIBLE AND THEY ARE ALSO KNOWN TO HOW MITOCHONDRIA DNA DAMAGE . LOW AUDIO DAMAGE LOW ODD. gtgt I THINK IN GENERAL, PEOPLE WHO TREAT CELLS WITH DRUGS THAT CAUSE INCREASE IN OXIDATIVE STRESS I THINK IN THOSE CASES WELL, IN MANY CASES WE.

SEE MITOCHONDRIAL DAMAGE. DEPENDING ON THE CELL SYSTEM AND OTHER SYSTEMS, YOU MIGHT FIND INCREASE IN MITOCHONDRIAL LEAPT BECAUSE THERE IS ALSO THIS OTHER SYSTEM THAT WORKS WITH CALLED STRESS INDUCED HYPERFUSION WHERE CERTAIN TYPES OF STRESS LEAD TO INCREASE IN MITOCHONDRIAL FUSION. SO I GUESS IT’S NOT CLEAR. BUT USUALLY INCREASING OXIDATIVE STRESS IS THOUGHT TO INCREASE LEVELS OF MITOCHONDRIAL MUTATIONS. I THINK THAT CERTAINLY CAN LEAD TO DEGENERATIVE DEFECTS. gtgt SO I THINK WE CAN CONTINUE THIS IN THE RECEPTION. HE WILL BE AVAILABLE RIGHT AFTERWARDS IN THE LIBRARY.

Headaches Migraines Numbness Loss of Speech DavisSpineInstitute

Amanda when you originally presented to the office, you presented with chronic neck pain, intense migraine headaches, compromise of speech, loss of sensation in the right arm, loss of sensation in the right leg. You were literally a shut in, you couldn’t work, couldn’t do anything. Why don’t you go ahead and tell me your story what was going on before you presented to Davis Clinic and what’s been your experience since receiving the specialized care here at Davis Clinic office, and how are you doing today with your lifestyle and.

Career Well before I came to the Davis Clinic, I was in the emergency room on three separate occasions. Each time I received care and treatment for migraine or tension headaches. Basically the doctors looked at me and said there’s not much we can do for you. We can put you on some really intense medicines and they gave me some prescriptions which either made me sick or didn’t work. I was on three different prescriptions, one from each visit. After that I still wasn’t getting any better. It had been a couple of weeks and I was still.

Pretty much just trapped in my house sleeping in my bedroom. I couldn’t drive for fear of my right side going numb. It was very tingly, the sensation was completely gone on my right side and I couldn’t talk at times which was extremely frustrating. So I had met up with some girlfriends for a birthday dinner and they had asked what was going on. A couple of them have migraines themselves. They had said that they had seen chiropractors for the relief from the migraine pain because their prescriptions were also not doing them.

Any good except for making them sick. So upon their advice I came to the Davis Clinic here and the protocols I received were DRS, EMS, Health Flight adjustments, and a series of supplements that I take a few different times of day. Now one more thing, everything we’ve done here it was non toxic. It was safe effective and natural as far as the health care correct Yes the supplements are all natural they’re vitamins for your bones to make them healthier and stronger. Ok and your nervous system as well. Yea! So in a nutshell is it safe to.

Say the treatment was effective as far as relieving the chronic migraine headaches and really getting the right side of body and speech back to a working state correct It did, I no longer have any numbness, I obviously have full use of my speech, I have little or no headaches. If I do have a headache I would guess right now it’s from the pollen outside. So it’s fair to say that we got you back to an active lifestyle, back to your duties as a caring mother to your three year old, and really just getting you back on track.

Animation Detecting diabetic retinopathy through a dilated eye exam

The comprehensive dilated eye exam opening the door to preventing blindness a doctor can detect signs of diabetic retinopathy during a comprehensive dilated eye exam the patient receives special eye drops to dilate the pupils the pupils open wide allowing the doctor to see the back of the eye clearly when eyes are dilated the doctor can clearly see the retina optic nerve and the macula early diabetic retinopathy starts with small red dots called micro aneurysms and can progress to leaking blood vessels causing thickening of the retina and blurring of vision or new blood vessel.

Growth that can bleed and cause blindness if you have diabetes you are at risk for diabetic retinopathy dilation enables doctors to get a better view of the back of the eye which allows them to determine whether there are early symptoms of disease but it’s important to know that all people older than 60 need a comprehensive dilated eye exam each year and should inform their doctor right away if they begin to have problems with their site people at higher risk may need to have a dilated eye exam more often.

Students Who Are Deafblind Using APH Products

Chapter 1 upbeat guitar music upbeat guitar music gtgt male announcer APH presents a Homegrown Tutorial featuring students who are deafblind gtgt Hello, my name gtgt Hello, my name is Cathy Nelson with the teacher training program at the University of Utah. During the next several minutes, you’re going to meet four young people who are deafblind. Deafblindness is defined as a concomitant hearing and visual impairment, the combination of which causes such severe communication and other developmental and educational needs that they cannot be accommodated in special education programs for children with deafness.

Or children with blindness. or children with blindness. The young people you are about to meet range in age about to meet range in age from 2 to 15 years, and like all individuals in society, are a diverse group. They have varying ability levels and different interests. Each individual in this tutorial Each individual in this tutorial has a different cause as well as a different level of vision and hearing loss. Each is unique and has a unique way of learning. Regardless of age, ability level, or interests, students who are deafblind.

Can and do learn. In this tutorial, you will see and hear how these students use and benefit from a variety of educational materials from the American Printing House for the Blind. The materials you see them using are appropriate for their age, ability levels, and interests ability levels, and interests and may also be appropriate for students in your classroom who are deafblind or who are visually impaired with additional disabilities. While watching each student, please keep in mind the impact that deafblindness, the dual sensory loss, has on development.

And learning, communication, access to information, and the student’s ability to interact with materials. The first child I’d like to introduce you to is twoyearold Blake. Let’s listen as his early interventionist, Melissa, tells us a little bit about Blake. gtgt Blake’s vision loss, he is diagnosed with Cortical Vision Impairment. He is also diagnosed with right ear neuropathy. His vision loss is more of how the information gets to the brain, so we have to teach him how to see, how to look. I give him a lot of tactual clues.

If I want him to move his leg, I’ll push his leg or touch his foot. I give him a lot of sound cues too. I give him a lot of praise. He does well with praise. How he communicates back is, he does a lot of vocalizations. gtgt Melissa told us that Blake has been diagnosed as having CVI or Cortical Visual Impairment. For more information on CVI, you may visit the APH website at the APH website at And click on the APH CVI website button. And now I’d like for you.

To meet Samuel. Samuel is eight years old Samuel is eight years old and attends public school. Amy is Samuel’s Amy is Samuel’s classroom teacher. gtgt Samuel was diagnosed with CHARGE syndrome, which he does have a vision and hearing impairment. and hearing impairment. He uses his vision very well. We do not know exactly how much he does hear, but he wears a hearing aid during the day, and we use an FM system during instructional activity. Samuel currently uses the Samuel currently uses the On the Way to Literacy books.

We’ve just introduced him to those. Recently this year, he had some literacy goals put into his IEP. put into his IEP. Samuel uses an object schedule or a calendar box all day long to let him know where he’s supposed to be, what activities he’s supposed to be doing. It helps him to transition throughout the day, so when we use the On the Way to Literacy books, we usually try to put an object in the calendar box related to the book so that he can know that he’s going to go sit down.

At the desk and read the book, and then he can get the book and kind of relate it to him. We use signs and real objects as much as possible as well as voice and words. Receptively, he understands several functional signs several functional signs very well. Expressively, he uses his own gestures and vocalizations that people close to him can interpret. We do coactive signing with him as well as getting him to model signs. gtgt Next, let’s meet 15yearold Lynn and her mother, Ann, as Ann talks about Lynn’s.

Vision and hearing impairments. gtgt Lynn was two years old when she was diagnosed when she was diagnosed with cancer of the retinas, and both eyes were removed, so she has no vision at all. so she has no vision at all. She had chemotherapy for the cancer, and it was an ototoxic chemotherapy, so it damaged chemotherapy, so it damaged her hearing. She has bilateral hearing loss She has bilateral hearing loss from the chemotherapy. She wears hearing aids in both ears when she goes to school or when it’s important that.

She differentiates sound, conversation. Lynn’s speech had started to develop. She didn’t have a lot of vocabulary, of vocabulary, but she was actually bilingual in Yupik Eskimo and English before using the chemotherapy, before using the chemotherapy, so she had her speech at least started before her hearing loss. I mean, we have several goals for Lynn. The first is to advance her vocabulary, her social skills, her mathematical skills, you know, anything dealing with education as well as reading. gtgt We’ll come back to Lynn and her mother later. Next is 12yearold Tyler.

He’s faced some unique challenges of his own. Stephanie and Kurt talk Stephanie and Kurt talk about their son Tyler’s about their son Tyler’s deafblindness, his cochlear implant, and some of their goals for Tyler. gtgt I’m Stephanie Kavanaugh. gtgt And I’m Kurt Kavanaugh. gtgt both And who are you gtgt I’m Tyler Kavanaugh. gtgt Tyler’s 12 12, and he was born blind and deaf. When Tyler was born, we were told initially we were told initially that he was anophthalmic, meaning without eyes, that he would see nothing, that he was profoundly deaf,.

That he was profoundly deaf, would hear nothing, and shortly after he was born, we noticed that he would flinch when we took flash pictures of him and reacting with his head, so we knew there must be something there, and we just decided to keep up with it, because when he was about five, he had tubes put in both ears because of a large number because of a large number of ear infections, and he came out of the tube surgery hearing nothing. I mean, we thought there wasn’t.

Much to lose. He lost all of it, so we immediately ran to our local cochlear implant surgeon local cochlear implant surgeon and said, We need to be and said, We need to be assessed right now because we have no way to communicate with this child. We were so used to speaking and having him listen, in his way, and respond that we were just frantic. So he was assessed, and he was implanted when he was 5 12 when he was 5 12 and very, very quickly took to his implant,.

But his speech really, really came along very rapidly after that. gtgt Like, whoa. gtgt It’s really interesting now how our goals have kind of progressed along with Tyler, because, in the beginning, when he was very little, our goals for him were for him to be healthy and to be able to hear us well enough to communicate, then they were to sign, then they were to speak, then they were to go to school, and now he’s been in the gifted program in public school program in public school.

Since third grade. I think our goals are sort of advancing just ahead of Tyler, but certainly now, they’re for him to go to college. gtgt Now that you’ve met our four gtgt Now that you’ve met our four students, we’d like for you to see how they use and benefit to see how they use and benefit from a variety of APH products from a variety of APH products and materials. Twoyearold Blake receives individual early intervention services from a vision specialist in his home and participates in a small activities group.

Vision specialist Melissa talks about their goals and some intervention strategies she uses with Blake as he uses APH products. gtgt With the Light Box, I was really trying to get him to just look at the Light Box, to just look at the Light Box, be aware of the light. He’s very aware of the light. He’s very aware of the light. You can tell. He gives you a response. It’s a real quick response, but as soon as a light comes on, you know, you’ll see him make a reaction.

But with the Invisiboard, But with the Invisiboard, again, just having him localize, doing just a tad bit of shift gaze between two objects. gtgt As with all children with motor impairments, it is critical to provide it is critical to provide appropriate support to assist with stability and positioning with stability and positioning so that vision can be accessed. Appropriate positioning will vary with each child, so it’s important to find the positions that best allow each student to maximize any vision potential. As Melissa told us, she uses the Light Box.

With Blake to provide maximum contrast for the objects he’s interacting with and to help him direct his gaze. and to help him direct his gaze. The green overlay is used with the Light Box because green is the color that Blake prefers. The Invisiboard also provides good contrast for Blake and blocks out visual clutter from the environment as he looks at objects as they move into his visual field. The unique characteristics of The unique characteristics of the Revolution and RibItBalls make them favorite products to use as intervention tools.

At the park. The bell inside the Revolution Ball continues to sound for approximately 20 seconds after it stops rolling, after it stops rolling, which can help Blake know which can help Blake know where the ball is. The RibItBall’s colors were designed specifically for children with Cortical Visual Impairment in mind. In addition, the inflatable RibItBall has ribs which make it easy for a child to grasp. It also has a unique crinkly sound when grasped which provides a nice auditory feedback. An activity with the balls provide opportunities for turntaking.

And other interactive skills. Now let’s join Samuel again as Amy begins to introduce the On the Way to Literacy books into his school program. into his school program. gtgt Okay, are you ready gtgt Okay, are you ready Can you open the book for me, please, Samuel Let’s use those hands. Let’s use these hands. Let’s use these hands. Open that book for me, buddy. Open that book for me, buddy. Open it, no. Right now, Samuel uses the On the Way to Literacy books during our morning routine when students are expected.

When students are expected to sit down and look through books as we get our backpacks books as we get our backpacks put away, so he does show interest in those. Now, we use them mainly just as well as the rest of our classjust to expose him to literacy, which is, you know, literacy, which is, you know, related to our curriculum that is expected to be taught here. As far as the literacy As far as the literacy activities, we really just want Samuel to attend to the book,.

Samuel to attend to the book, attend to the task, to participate by turning the pages and feeling the objects, and we also want him to show some comprehension between the sign and the real objects and the topic of the book, so. gtgt After reading The Littlest Pumpkin book, The Littlest Pumpkin book, Samuel enjoys the corresponding puzzle. Let’s take a look as Samuel works to complete The Littlest Pumpkin puzzle. gtgt Can you do the puzzle Where’s the pumpkin Let’s do the pumpkin puzzle, okay Look right here. Take out the mouth.

And the nose and his two eyes. You got them Okay, now you have to put it together. You can put the pieces You can put the pieces in the puzzle. Let’s put them in, okay It’s hard, isn’t it There. There. Okay, where’s his nose Let’s find his nose. Where is his nose There you go. Good job. Push, push it down. I’m helping you. All on your own. Good job. Good job. All right, now where does the pumpkin go does the pumpkin go Where does his face now that he has his face,.

Where does the pumpkin go Yeah, there you go. All right, push him in there. gtgt As we’ve seen, Amy uses sign language and speech together to communicate together to communicate information to Samuel, but notice that Amy introduces the reading activity to Samuel the reading activity to Samuel by also using a calendar box system, providing him with another cue about the activity that is about to take place. that is about to take place. Because literacy opportunities have only recently been written into Samuel’s IEP, his expected level of participation is that.

He will tactually and visually explore the pages of The Littlest Pumpkin book and will turn the pages as appropriate. Amy also asked Samuel to respond to some simple requests such as find the pumpkin. During the pumpkin puzzle activity, Samuel finds the correct puzzle pieces requested and places it into place with some gentle assistance from Amy. Depending upon the goals Depending upon the goals for your student, you will have different expectations for how the student uses materials, such as On the Way to Literacy books. This is a starting point.

For Samuel. for Samuel. Lynn, on the other hand, has been a braille reader for a few years, and her for a few years, and her literacy skills allow her to read for leisure. Here Lynn is reading Here Lynn is reading Looking Out for Sarah from the duPont Series PrintBraille Books with her mother. gtgt In sweet. gtgt In sweet. gtgt Tones. gtgt Tones. gtgt Mmhmm. gtgt What’s on there gtgt There’s Sarah sitting on her bed, and there’s a picture of a big black dog, and he’s licking her on the chin.

Gtgt What color is his ears gtgt His ears are black too. They’re the same color as he he’s black all over. gtgt Although Lynn is a braille reader, she benefits from assistance from her mother, especially when reading books especially when reading books with new vocabulary. gtgt Land in her lap. gtgt Land in her lap. gtgt Mmhmm, his paw landed in her lap. in her lap. gtgt Sometimes Lynn enjoys using her braille skills to play games such as Web Chase, an originally designed board game by APH to help develop.

Important tactile skills within a fun, recreational context. During the course of the game, Lynn practices reading, tactual Lynn practices reading, tactual scanning, directionality, counting, following directions, and other important skills. and other important skills. gtgt What’s on the round ones gtgt What’s on the round ones Huh gtgt Butterfly. gtgt Butterfly. gtgt A butterfly. gtgt A three. gtgt A three. gtgt Mmhmm. Because you have to count the lines. gtgt One. gtgt One. gtgt Go on around. Lift your elbow up just a little bit. Let’s bring the game board.

To you. What’s that gtgt One. gtgt Okay. gtgt Two. gtgt Mmhmm. gtgt Three. gtgt Tyler is a proficient braille reader and writer. This level of skill does not come easily does not come easily for a child who’s deafblind. Before braille proficiency, there was a lot of work there was a lot of work for Tyler and his parents. Let’s listen as Stephanie and Kurt talk about Tyler’s early introduction to literacy using APH’s On the Way to Literacy series of books. gtgt And also very early on, we were very, very fortunate.

To acquire a whole set of On the Way to Literacy books, the braille tactile books, all but one of which we have now all but one of which we have now passed on to other kids, passed on to other kids, but we’re keeping Something Special, oh, for sentimental reasons and so his younger siblings can have an idea of what it is that Tyler was working with when he was little as compared to the kinds of books they had when they were small. gtgt I should tell, we read those a lot.

Gtgt They were wonderful, wonderful books. wonderful books. I mean, they’d probably I mean, they’d probably be great for any kid. be great for any kid. He just happened to be the first one and the one who’d benefit from them most. from them most. What else did we do What else did we do You were sleeping. But I have no doubt that these books started him on the way to a love of reading, and, for a number of reasons, reading has just been his thing. gtgt Did you hear what Stephanie.

Said about the On the Way to Literacy books leading to Tyler’s love of reading It’s a pretty strong It’s a pretty strong endorsement. endorsement. Just as reading to sighted and hearing children at an early age is important, early literacy exposure is critical for children who are deafblind. Tyler also had early experiences with the APH Light Box and materials. As Stephanie and Kurt tell us, Tyler learned many invaluable skills with the Light Box. gtgt When Tyler was very small, we propped him up in a little chair in front of the Light Box,.

Chair in front of the Light Box, and we had the APH Light Box and I think three sets of materials that went with those, and so one of the first things we did with Tyler is, we would put up a little gel with a picture of an object for example, a blue cupand then we would get a blue cup, and Tyler would put his face and Tyler would put his face right down near it, and we’d say, Tyler, that’s a picture of a blue cup. Tyler, here’s a blue cup..

Optic Nerve Cut During Eye SurgeryNY Medical Malpractice

Welcome, and thank you for joining me. I’m Gerry Oginski, a New York Medical Malpractice and Personal Injury Trial Lawyer practicing law here in the state of New York. Today’s tutorial tip explains one solution that I was able to achieve for an injured victim. Here’s what I mean. A gentleman was walking down the street in Brooklyn one day when he was physically attacked. He was hit and punched in the face and as a result suffered fractures to the lower part of his eye known as the orbit. When he was taken to the hospital he was told that he had a fracture of his orbit and that.

He would probably need surgery to fix it. That would have been fine except there was one problem. As a result of the fracture the muscle that controlled his eye movement happened to be trapped and stuck inside of it because of the viscous nature of the attack. This gentleman who had previously excellent vision, still had good vision except there was one problem. The muscle that controlled his eye movement was now stuck so now his eye pointed out to the side. The patient agrees to undergo this surgery thinking based upon the doctor’s reassurances that it’s a relatively simple procedure and.

She’s done this many times. After the surgery is performed the patient is given a patch and told to come back the next day, which he does. The doctor takes the patch off in the office and says, Okay what do you see He said, Did you take the patch off She said, What do you mean He couldn’t see anything. She immediately sends him back to the hospital for an MRI. The MRI comes back and he is told, You need surgery now. The patient goes back into surgery later that.

Day in an attempt to fix whatever problem the doctor noticed but didn’t exactly tell the patient before undergoing the second procedure. He’s given a patch again, told to come back the following day now, which he does. It’s the second procedure, the day after the procedure. The doctor takes the patch off and says, What do you see The patient says, Nothing. He said, What do you mean, nothing Patient came to me because he was concerned that something had gone wrong that the doctor did not fully explain to him.

What I learned during the course of the investigation was that during the first surgery the doctor used a titanium implant to connect the broken bone fragments together. Unfortunately, she cut off the optic nerve, which is the nerve that controls the vision but didn’t recognize it. When she saw the MRI the following day she recognized that this implant, this titanium device, which is meant to hold the fragments in was literally transecting and cutting the area where the optic nerve was. Despite her attempts the next day to go ahead and move that implant it was useless because.

Of the permanent damage had already occurred. What was supposed to be a simple procedure turned out to be a devastating, lifealtering procedure for this gentleman. We learned later when I had a chance to question the doctor at her deposition was that she had only done this procedure less than a handful of times. Immediately before jury selection was scheduled the defense recognized that they had significant problems and entered into settlement negotiations at that time. I’m pleased to say that as a result of those settlement negotiations we were able to successfully resolve the case to my clients satisfaction.

Leadboard Category: Neuropathy Home Remedy

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