NBIO Presents: Christopher Fortenbach, MD, PhD, (University of Washington, Department of Ophthalmology)

Photochemical Vision Restoration in Outer Retinal Degeneration 

Age-related macular degeneration and retinitis pigmentosa are the most common causes of blindness in high-income countries. These forms of outer retinal degeneration result in progressive loss of photoreceptor cells while the inner retina largely remains structurally intact. While current therapies to address this vision loss are limited, a promising strategy involves the intravitreal injection of small molecules known as photoswitches. These photochemical ligands restore light-mediated responses by binding to surviving inner retinal neurons and blocking ion channels in a conformation-dependent manner. Upon absorbing light of a particular wavelength, they undergo a cis-trans isomerization, resulting in a light-dependent electrical response that can be conveyed to downstream neurons. Unlike surgical implants or viral-mediated gene therapies, photoswitches are titratable and upgradable as newer therapies become available. My laboratory develops and studies a novel class of photoswitches designed to target upstream retinal neurons and restore retinal signaling. We investigate the mechanisms by which these ligands act on the retina using a combination of electrophysiological techniques, and we quantify the retina’s encoding capacity in response to visual stimuli. Ultimately, by improving our understanding of how photoswitch structure influences the restoration of retinal signaling, we aim to design better therapies that more closely mimic native visual signaling.