SS31 protects damaged retinal cells through the AMPK/DRP1 signaling pathway.

PURPOSE: Glaucoma is a group of neurodegenerative diseases characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Mitochondrial dynamics contribute to the maintenance of neuronal homeostasis, and abnormalities can lead to the development of glaucoma. SS31 is a mitochondria-targeting short peptide that has been found to protect mitochondrial function and thereby protect damaged retina-associated cells. The aim of this study is to investigate whether SS31 protects damaged retinal cells by activating the AMPK/DRP1 pathway. METHODS: The relationship between SS31 and oxidative stress was determined by live-cell imaging. The cells were inoculated in the well plate and treated with H2O2 (150 μM) for 24 h and pretreated with or without SS31 (100 nM), AICAR (17.5 μM), or dorsomorphin (7 μM) for 2 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) were used to evaluate cell viability. Mitochondrial genetic stability was detected by droplet digital PCR. The expression of AMPK and DRP1 was detected by western blot. In addition, intraocular pressure and retinal thickness were evaluated in mice with acute ocular hypertension. RESULTS: SS31 inhibited H2O2-induced cell death of 661W through the AMPK signaling pathway and maintained mitochondrial genetic stability. SS31 regulates AMPK/Drp1 signaling in 661W cells after oxidative stress. SS31 reduced intraocular pressure and maintained normal retinal thickness in mice with acute ocular hypertension. CONCLUSIONS: SS31 regulates mitochondrial dynamic network remodeling by activating AMPK/DRP1 signaling pathway and protects retinal-related cells.