| First Author | Zhou Q | Year | 2017 |
| Journal | Mol Cell Biol | PubMed ID | 28584193 |
| Mgi Jnum | J:244227 | Mgi Id | MGI:5913006 |
| Doi | 10.1128/MCB.00001-17 | Citation | Zhou Q, et al. (2017) Let-7 contributes to diabetic retinopathy but represses pathological ocular angiogenesis. Mol Cell Biol |
| abstractText | The in vivo function of microRNAs (miRNAs or miRs) in diabetic retinopathy (DR) and age-related macular degeneration (AMD) remains unclear. Here we report that let-7 family members are expressed in retinal and choroidal endothelial cells (EC). In ECs, overexpression of let-7 by adenovirus represses EC proliferation, migration, and networking in vitro, while inhibition of the let-7 family with a locked nucleic acid (LNA)-anti-miR has the opposite effect. Mechanistically, silencing of the let-7 target gene HMGA2 mimics the phenotype of let-7 overexpression in ECs. Let-7 transgenic (let-7-Tg) mice show features of non-proliferative DR, including tortuous retinal vessels and defective pericyte coverage. However, these mice develop significantly less choroidal neovascularization (CNV) compared to wildtype controls after laser injury. Consistently, silencing of let-7 in the eye increased laser-induced CNV in wild-type mice. Together, our data establish a causative role of let-7 in non-proliferative diabetic retinopathy and a repressive function of let-7 in pathological angiogenesis, suggesting distinct implications of let-7 in the pathogenesis of DR and AMD. |
