MicroRNA-184 Promotes Differentiation Of The Retinal Pigment Epithelium

Dedifferentiation of retinal pigment epithelium(RPE)cells is a crucial contributing factor to the pathology of retinal degenerative diseases,including age-related macular degeneration(AMD).Herein,we aim to reveal the roles of microRNAs(miRNAs)in RPE dedifferentiation and seek for potential therapeutic targets.Based on the microarray data,mi R-184 was sorted out as the most up-regulated signature along with the differentiation from human induced pluripotent stem cells(hiPSC)to RPE cells,suggesting its potential promotive role in RPE differentiation.In vitro study indicated that miR-184 insufficiency suppressed RPE differentiation,typified by reduction of RPE markers,and promoted cell proliferation and migration.The role of miR-184 in maintaining regular RPE function was further proved in zebrafish studies.We also noticed that miR-184 expression was reduced in the macular RPE-choroid from a donor with RPE dysfunction compared to a healthy control.We next demonstrated that RAC-beta serine/threonine-protein kinase(AKT2)was a direct target for miR-184.MiR-184 promoted RPE differentiation via suppression of AKT2/mammalian target of rapamycin(mTOR)signaling pathway.We also found that AKT2 was up-regulated in macular RPE-choroid of the donor with RPE dysfunction and dry AMD patients.Taken together,our findings suggest that mi R-184 insufficiency is involved in the pathogenesis of dry-AMD.MiR-184 promotes RPE differentiation via inhibiting the AKT2/mTOR signaling pathway.MiR-184 based supplementary therapeutics and mTOR blocker,like rapamycin,are prospective options for AMD treatment.