Cause of cone death discovered in retinitis pigmentosa

Boston-Research conducted at the angiogenesis laboratory at Massachusetts Eye and Ear Infirmary (MEEI) has identified the mode of death of cone photoreceptor cells in an animal model of retinitis pigmentosa (RP).

The study was published in the Proceedings of the National Academy of Sciences Early Edition.

The study, led by Demetrios G. Vavvas, MD, PhD, a physician-scientist in the retina service of MEEI, and an assistant professor of ophthalmology at Harvard Medical School, and including Joan W. Miller, MD, MEEI/Massachusetts General Hospital chief of ophthalmology and chairwoman of ophthalmology at Harvard Medical School, further identified the receptor-interacting protein (RIP) kinase pathway as a potential target for developing treatment for vision loss in patients with retinitis pigmentosa.

Previous studies have identified mutations in more than 50 genes that cause RP, but the mechanisms by which rods and cones die remain to be completely defined. Because many of the genes associated with RP produce proteins that are used specifically in rod cells, it is still a puzzle why and how cones-which in some cases do not use the mutant proteins-die after rods degenerate.

Using a mouse model of RP, the investigators studied whether RIP-kinase-mediated necrosis is involved in the death of photoreceptor cells, finding for the first time that it is involved in cone degeneration and that a deficiency of RIP kinase reduced cone loss. Moreover, the study found that treatment with a drug that inhibits RIP kinase significantly delayed cone cell death and preserved cone photoreceptors.

“Though the precise mechanisms involved in RIP-kinase-inducing necrosis remain unknown, our finding that necrosis results in cone cell death puts us one step closer to understanding this disease and, more importantly, moves us one step closer to being able to provide novel therapies to millions of patients with vision loss,” said Dr. Vavvas.

Dr. Miller is an associate medical editor on the Editorial Advisory Board of Ophthalmology Times.

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