Enzyme Calcineurin Contributes to Glaucoma and Use Drug to Block Retinal Ganglion Cell Death

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Eye Conditions - Glaucoma

Glaucoma causes blindness by killing retinal ganglion cells, the cells that make up the optic nerve. The biggest risk factor for developing glaucoma is elevated intraocular pressure, but lowering the pressure alone does not always stop the progression of this blinding disease. Research is underway to identify why the retinal ganglion cell dies and to find ways to stop retinal ganglion cell death. Scientists at the Massachusetts Eye and Ear Infirmary (MEEI) are a step closer to solving the mystery. They have discovered that that an enzyme, calcineurin, contributes to retinal ganglion cell death in animal models and have used a drug to inhibit the death of these cells. Their findings are posted on the Proceedings of the National Academy of Sciences online early edition the week of Aug. 8.

According to Cynthia L. Grosskreutz, M.D., Ph.D., senior author of the study and co-director of the Glaucoma Service at MEEI, neuroprotection as a strategy has been proposed as an adjunctive approach to pressure lowering in glaucoma, but target candidates have been elusive.

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"In glaucoma, we know that the disease progresses because the retinal ganglion cells die. Our goal is to figure out what mechanisms govern this cell death and to develop a strategy for protecting the cells from the things that cause them to die," she explained. "In the studies reported in this paper, we use animal models of glaucoma to identify calcineurin as a contributor to retinal ganglion cell death in experimental glaucoma. We were able to use the drug FK506 to inhibit calcineurin and observe significant protection of the optic nerve and retinal ganglion cells."

The research results suggest that calcineurin activation and cleavage may play an important role in glaucomatous optic nerve degeneration and point to a specific molecular target in retinal ganglion cells that may be amenable to therapeutic intervention such as the use of drugs like FK506. This is the first time this particular enzyme was identified as a cause of retinal cell death in glaucoma.

"Better understanding of how and why the retinal cells die can help us develop better treatments for this disease, which affects more than 66 million people worldwide and is the leading cause of irreversible blindness," Grosskreutz said. - Boston

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