The Expression of Parthanatos Markers and miR-7 Mimic Protects Photoreceptors from Parthanatos by Repressing a-Synuclein in Retinal Detachment

Retinal detachment (RD) refers to the separation between the neuroepithelium and the pigment epithelium layer. It is an important disease leading to irreversible vision damage worldwide, in which photoreceptor cell death plays a major role. cc-Synuclein (cc-syn) is reportedly involved in numerous mechanisms of neurodegenerative diseases, but the association with photoreceptor damage in RD has not been studied. In this study, elevated transcription levels of cc-syn and parthanatos proteins were observed in the vitreous of patients with RD. The expression of cc-syn-and parthanatos-related pro-teins was increased in experimental rat RD, and was involved in the mechanism of photoreceptor damage, which was related to the decreased expression of miR-7a-5p (miR-7). Interestingly, subretinal injection of miR-7 mimic in rats with RD inhibited the expression of retinal cc-syn and down-regulated the parthanatos pathway, thereby protecting retinal structure and function. In addition, interference with cc-syn in 661W cells decreased the expression of parthanatos death pathway in oxygen and glucose deprivation model. In conclusion, this study demonstrates the presence of parthanatos-related proteins in patients with RD and the role of the miR-7/cc-syn/parthanatos pathway in photoreceptor damage in RD. (Am J Pathol 2023, 193: 1833-1844; https://doi.org/10.1016/j.ajpath.2023.06.011)