Restoring Sight in Photoreceptor Degeneration

For over a century, the retina was thought to only use a unidirectional circuit to process visual information: photoreceptor cells called rods and cones convert light into electrical signals, which are analyzed by second-order cells before reaching retinal output cells called ganglion cells, which then signal to higher brain areas to produce conscious visual perception. This simple view became more complicated in 2002 when some ganglion cells were found to function as photoreceptors.

Named intrinsically photosensitive retinal ganglion cells (ipRGCs), these novel photoreceptors drive subconscious physiologic responses to light such as pupil constriction, enhancement of alertness, and regulation of sleep/wake timing. In a previous NIH-funded project, Kwoon Y. Wong, Ph.D., and his students discovered that ipRGCs signal not only out of the retina, but also intraretinally to second-order cells called amacrine cells. Unlike most neural circuits, this “backward” signaling pathway does not utilize neurotransmitters; instead, ions diffuse from ipRGCs to the amacrine cells through intercellular channels called gap junctions.

Dr. Wong has been awarded an NIH R01 grant to elucidate the structure and function of this unusual circuit. Because this circuit remains light-sensitive in rod/cone-dystrophic retinas, studies of its properties could lead to innovative strategies for restoring sight in patients suffering photoreceptor degeneration.