Misfolded Proteins and Retinal Dystrophies
Many mutations associated with retinal degeneration lead to the production of misfolded proteins by cells of the retina. Emerging evidence suggests that these abnormal proteins cause cell death by activating the Unfolded Protein Response, a set of conserved intracellular signaling pathways that detect protein misfolding within the endoplasmic reticulum and control protective and proapoptotic signal transduction pathways. Here, we review the misfolded proteins associated with select types of retinitis pigmentosa, Stargadt-like macular degeneration, and Doyne Honeycomb Retinal Dystrophy and discuss the role that endoplasmic reticulum stress and UPR signaling play in their pathogenesis. Last, we review new therapies for these diseases based on preventing protein misfolding in the retina.
KeywordsEndoplasmic Reticulum Retinal Pigment Epithelial Unfolded Protein Response Retinitis Pigmentosa Retinal Degeneration
We thank Victory Joseph for helpful comments. This work was funded by NIH grants EY01919, EY06842, EY02162, EY018313; the Foundation Fighting Blindness; and RPB.