Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
J Cell Physiol. 2019 Aug;234(8):14100-14108. doi: 10.1002/jcp.28100. Epub 2019 Jan 12.
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.
视蛋白突变与常染色体显性遗传型色素性视网膜炎（RP）有关。在这里，我们报告了一位患者同时发生与视蛋白（R135W）新突变相关的 RP 伴双侧小眼球和急性闭角型青光眼。用 myc 标记的野生型（WT）和 R135W 视蛋白构建体转染 ARPE-19 细胞。通过环己酰亚胺追踪分析分析 WT 和 R135W 视蛋白的半衰期。我们发现 R135W 视蛋白在内质网（ER）中积累，并诱导未折叠蛋白反应（UPR）和细胞凋亡。此外，伴侣 HSP70 通过减轻 UPR 信号减轻 ER 应激并预防 R135W 视蛋白诱导的细胞凋亡。这些发现揭示了 RP 的新发病机制，并表明伴侣 HSP70 对视蛋白具有潜在的治疗意义。
