MiR-1246 promotes anti-apoptotic effect of mini-αA in oxidative stress-induced apoptosis in retinal pigment epithelial cells.

Abstract

Geographic atrophy (GA) is a late-stage symptom of an age-related macular degeneration (AMD), characterized by the loss of retinal pigment epithelial (RPE) cells and photoreceptor functions. Despite being a major cause of blindness in individuals of 65 years of age and older, some forms of AMD, including GA, still lack targeted treatment. Our previous study demonstrated that mini-αA peptide, which contains the functional site of αA-crystallin, protected RPE cells from NaIO3 -induced apoptosis. To further investigate the underlying mechanism, we applied next-generation sequencing analysis to identify miR-1246 as a putative mediator of mini-αA protective function. To investigate the role of miR-1246 in RPE cell apoptosis, a stable miR-1246-low-expression cell line was established by using miR-1246 inhibitor. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate the proliferation of RPE cells, mRNA and miR-1246 expression were detected by the quantitative reverse transcriptase-polymerase chain reaction. We have further identified caspase-3 and caspase-14 as molecular targets of miR-1246 involved in regulation of apoptosis in NaIO3 -incubated cells. Interestingly, disruption of miR-1246 expression enhanced anti-apoptotic effect of mini-αA on RPE cells during oxidative stress. Our results provide a mechanistic basis for evaluation of miR-1246 as a new candidate target for the clinical treatment of AMD.