Candidate photoswitch drugs for restoring visual function in blindness

• Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are degenerative blinding diseases caused by the death of rods and cones in the retina, leaving the remainder of the visual system intact but unable to respond to light.
• Photoswitches can restore light sensitivity to the retina and behavioral responses to blind mice and rats models of RP.
• Ongoing studies are aimed at identifying the best photoswitch and optimal delivery method for safe, effective, and long-lasting vision restoration.

Functional plasticity in the degenerating retina

• Retinal ganglion cells (RGCs) become hyperactive as photoreceptors die, obscuring light responses initiated by remaining rods and cones.
• RGCs in degenerating retinas become permeable to large molecules, including photoswitch compounds. Hyperpermeability can be exploited for delivering drugs that reduce hyperactivity and photoswithces that confer light-sensitivity.
• We are investigating the molecular basis of these physiological changes. Specifically, how do RGCs know that photoreceptors are dying, and what occurs in the RGCs to make them hyperactive and hyperpermable?