Cone Opsin Determines The Time Course of Cone Photoreceptor Degeneration in Leber Congenital Amaurosis

It is been long known that ventral and central cones degenerate more rapidly than dorsal cones in retinoid-deprived LCA (Leber’s Congenital Amaurosis) models.  This paper in PNAS by Tao Zhang, Wolfgang Baehr

…and Yingbin Fu shows that SW-opsins, but not ML-opsin, aggregates to form cytoplasmic inclusions in mutant mice and transfected cells.  This result explains why blue cone function is lost earlier than red/green-cone function in patients with LCA.  They also show that substituting rhodopsin with S-opsin in Lrat−/− rods resulted in mislocalization and aggregation of S-opsin, ER stress, and dramatically accelerated rod degeneration.  According to these results, cone opsins may play a major role in determining the degeneration rate of photoreceptors in LCA.