Researchers in the WashU Medicine Department of Ophthalmology & Visual Sciences have discovered key neuroprotective genes that could lead to the development of gene therapies to treat retinitis pigmentosa, an inherited form of retinal degeneration that causes blindness. The findings, published in Neuron on April 9, point to new therapeutic strategies to maintain retinal health and protect against degeneration.
Led by first author Ning Shen, PhD, a staff scientist; Daniel Kerschensteiner, MD, the Bernard Becker Professor of Ophthalmology and Visual Sciences; and Philip Ruzycki, PhD, an assistant professor, the researchers performed a genome-wide CRISPR screen to look for genes whose loss worsened retinal degeneration in a mouse model of retinitis pigmentosa. They then developed and tested two gene therapies to boost the expression of the identified candidate genes — UFD1 and UXT — to promote the clearing of toxic proteins. Injection of either gene therapy to the eyes of mice with retinitis pigmentosa reduced photoreceptor death, maintained the light-sensing capabilities of the retina and preserved vision.
Likewise, delivery of either gene therapy to a human retinitis pigmentosa model developed by the Bright Center for Human Vision at WashU Medicine — using human donor retinas cultured in a dish — preserved photoreceptors, demonstrating strong therapeutic promise.
“This study bridges a critical bottleneck in translating laboratory-based findings to the clinic by leveraging both mouse and human models of retinitis pigmentosa to develop and test human-compatible gene therapies,” said senior author Kerschensteiner, who also leads the Bright Center for Human Vision. The genome-wide screen results, shared as a public resource, point to additional candidate genes for future therapeutic development to preserve vision.
