Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa

There are several diseases that cause people to lose their eyesight and become blind. One of these diseases, called retinitis pigmentosa, kills cells at the back of the eye known as rod cells. At first, it affects vision in low light and peripheral vision, but later it affects vision during the daytime as well. There are no effective treatments for patients with retinitis pigmentosa. Yet previous genetic studies have shown that disrupting the activity of genes in rod cells can slow the progression of the disease and preserve vision in mice. As for all genes, proteins called transcription factors regulate the activity of rod cell genes. Nakamura et al. now report the discovery of a small drug-like molecule, that they name Photoregulin3, which alters the activity of a transcription factor that regulates rod genes. In follow-up experiments, mice with a mutation that replicates many of the features of retinitis pigmentosa were given Photoregulin3 to see if it could slow the progression of the disease. Indeed, Photoregulin3 could stop many of the rod cells from degenerating in the treated mice. At the end of the experiment, the mice treated with this small molecule had about twice as many rods as the control mice. The treated mice also responded better to flashes of light. Nakamura et al. hope that the findings will one day benefit patients with retinitis pigmentosa. But first more research needs to be done before testing Photoregulin3 in humans. For example, the drug-like molecule needs to be made more potent, and if possible adapted to work when given orally, meaning patients could take it as a pill.