Department of Defense Recognizes Bascom Palmer MS Research Team

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Sanjoy Bhattacharya, Ph.D., who leads a research team at Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, has been investigating ways to prevent the vision loss associated with multiple sclerosis (MS). The research has led the team to a biological process, called deimination, that plays a key role in MS. This work was recently honored by the Department of Defense through their Congressionally Directed Medical Research Programs.

Multiple sclerosis is an autoimmune disorder, during which the immune system attacks the myelin sheaths that insulate neurons. Myelin acts like the rubber coating around electrical wires, and when it’s destroyed, neurons can have trouble transmitting information.

Dr. Sanjoy Bhattacharya

Over the years, Dr. Bhattacharya’s team kept finding heightened levels of deiminase, the enzyme that causes deimination, in the optic nerves of MS patients. Deimination is a protein modification that can have either good or bad effects, depending on where the deiminated protein is located.

Deiminase converts an amino acid, called arginine, into a related amino acid, called citrulline. These modifications permanently alter certain brain proteins. Inside neurons, deimination is important and useful, helping these long cells transport key molecules.

However, the brain contains many other cell types, such as astrocytes (astroglia), which support neuronal function. When these cells become inflamed, they can produce too much deiminase, when can generate a cascade of bad events.

“Deiminase is secreted by the astroglial cells and begins attacking the myelin sheath of the neurons and making more deimination,” said Dr. Bhattacharya, who is professor of ophthalmology and also directs the Ophthalmology Mass Spectrometry Facility at Bascom Palmer. “This leads to more myelin being chewed down by the protease enzymes, more peptide formation and more immunogenic activity.”

While too much deimination is happening on the outside of neurons, too little is happening on the inside, reducing protein transport and limiting neuronal function.

Dr. Bhattacharya believes restoring normal deimination could be the key to stopping MS-associated vision loss and possibly regenerating damaged tissue. His lab received a Multiple Sclerosis Research Award, Investigator-Initiated Research Award from Congressionally Directed Medical Research Programs to advance that work, and the agency recently highlighted his progress on its website.

“If you can make deimination optimal, that will lead to more efficient transport inside neurons,” said Dr. Bhattacharya. “That transport means the neurons are healthy.”

This research could also be applied to other diseases, such as Alzheimer’s and glaucoma. Understanding the mechanisms that drive deimination could lead to therapies that correct this faulty process, restore vision in MS patients and potentially treat these other neurodegenerative conditions.

 

 

 

 

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