Protein Misfolding and Potential Therapeutic Treatments in Inherited Retinopathies

Retinitis pigmentosa (RP) is a group of inherited retinopathies characterized by progressive peripheral vision loss that can subsequently lead to central vision loss. RP is one of the most common causes of registered visual handicap among those of the working age in developed countries, and currently it is estimated to affect 1 in 3,500 people worldwide. At the genetic level, RP is one of the most heterogeneous inherited conditions, segregating in autosomal dominant, recessive, or X-linked recessive modes, with approximately 40 genes having been implicated in the disease pathology (http://www.sph.uth.tmc.edu/RetNet). To date, there is a growing list of destabilizing mutations within retinal-specific or nonspecific genes (e.g., RHO, RPGR, RS1, BBS6, AIPL1, RDS-peripherin, and IMPDH1, etc.) that have been found to cause proteins to misfold and become aggregation-prone with subsequent loss of normal protein functions. In this minireview, we will briefly explore the role protein misfolding plays as a disease mechanism in autosomal dominant RP and also highlight potential therapeutic strategies for inhibiting protein aggregation in the retina.