Zhuo-Hua Pan, Ph.D.

Wayne State University School of Medicine - Visionary

Project title: "Developing an optogenetic approach for treating blindness caused by retinal degeneration"

 

Vision normally begins when rods and cones, also called photoreceptor cells, respond to light and send signals through other retinal neurons, interneurons, and the optic nerve to the visual cortex of the brain where visual images are formed.  Unfortunately, many inherited and acquired retinal degenerative diseases, such as retinitis pigmentosa (RP), involve degeneration and death of the rods and cones, leading to blindness. Age-related macular degeneration (AMD), a leading cause of blindness in the elderly, strikes the same photoreceptor cells in the retina.

Since photoreceptor cells do not regenerate after birth, once they have died, the only option for vision restoration would be to re-introduce new photoreceptor cells or replace them with other light sensors.

We are exploring a new strategy by genetically engineering retinal interneurons that are normally not photosensitive into photosensitive cells – thus restoring light-sensitivity to retinas that lack photoreceptors.  To implement our strategy, we borrowed a recently cloned gene from green algae. The gene codes for a light sensitive protein, called channelrhodopsin-2 (ChR2), that is present in the eye spot of green algae. This light-sensitive protein that is used by algae to detect light for guiding their behavior is similar to that used by rods and cones in humans, but its simple and unique properties make it possible to use this protein to engineer light-sensitive cells.

Our published studies have already demonstrated, as proof-of-concept, the feasibility of this new treatment strategy in animal models. Our ongoing and future studies will address the issues that are essential for moving this treatment strategy to clinical applications.