11-cis-retinal and Glaucoma--Angle-Closure

Rhodopsin mutations are associated with the autosomal-dominant form of retinitis pigmentosa (RP). Here we report simultaneous occurrence of RP associated with bilateral nanophthalmos and acute angle-closure glaucoma in patient with a new mutation in rhodopsin (R135W). ARPE-19 cells were transfected with myc-tagged wild-type (WT) and R135W rhodopsin constructs. The half-life of WT and R135W rhodopsin was analyzed via cycloheximide chase analysis. We found that R135W rhodopsin was accumulated in the endoplasmic reticulum (ER) and induced unfolded protein response (UPR) and apoptosis. Moreover, chaperone HSP70 alleviated ER stress and prevented apoptosis induced by R135W rhodopsin by attenuating UPR signaling. These findings reveal the novel pathogenic mechanism of RP and suggest that chaperone HSP70 has potential therapeutic significance for RP.

Topics: Adult; Apoptosis; Cell Line; Child; Child, Preschool; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Epithelial Cells; Exome Sequencing; Female; Glaucoma, Angle-Closure; HSP72 Heat-Shock Proteins; Humans; Hyperopia; Male; Microphthalmos; Middle Aged; Molecular Chaperones; Mutation; Pedigree; Retinal Pigment Epithelium; Retinitis Pigmentosa; Rhodopsin; Signal Transduction; Unfolded Protein Response