Jonathan H. Jonathan H. Lin, MD, PhD

University of California San Diego - New Invesitgator

Project Title: "Chemical and Genetic Manipulation of the Unfolded Protein Response to Prevent Retinal Degeneration"

 

The most common cause of inherited blindness is retinitis pigmentosa (RP), a family of diseases with various forms of inheritance caused by mutations in more than 45 genes. Over 100 distinct mutations have been identified in the rhodopsin gene that lead to RP. Many of these mutations cause rhodopsin protein misfolding. The cellular and molecular processes that link rhodopsin misfolding to photoreceptor cell death and retinal degeneration are not well understood. The Unfolded Protein Response (UPR) is a set of cellular signaling pathways that detects misfolded proteins and promotes cell survival by reducing misfolded protein levels. However, if protein misfolding persists, the UPR switches to promote apoptosis. Our previous studies show that UPR is activated in retinal degeneration arising from P23H rhodopsin. We hypothesize that we can artificially manipulate the UPR to prevent P23H rhodopsin misfolding and thereby enhance photoreceptor cell survival. These studies may offer a new way to prevent blindness arising from protein misfolding.