Defining the Pathway for Misfolded Protein Degradation in Retinitis Pigmentosa Caused by the Rhodopsin-P23H Mutation

Retinitis pigmentosa (RP) is a term used to describe a wide variety of inherited degenerative diseases that affect the eye. While there are many causes of this disease, the most commonly found mutation that causes RP in North America is an autosomal dominant missense mutation in rhodopsin (RhoP23H). Previous studies have shown that RhoP23H is predominantly misfolded, resulting in a dramatic loss of the ability to stably bind 11-cis retinal and thus function as a photopigment. Previous work has shown that this process is conserved to some degree across many models, from pigs to mice, and even is evident when mutant mammalian rhodopsin is exogenously expressed in flies. Presently, there is limited information on the mechanism(s) that detect and degrade rhodopsin. To investigate this phenomenon, we cultured transgenic Drosophila melanogaster and evaluated expression of exogenous rhodopsin through western blot analysis. Our results suggest that the fly system is capable of simulating a realistic environment for murine rhodopsin. By harnessing the powerful genetic tools surrounding the fly system, future studies using RNAi techniques may be able to elucidate identification and degradation pathways important to the progression of RP