SMALL AND DANGEROUS: MICRORNA-21 AND BLINDNESS

Abstract

Retinal neovascularization (RNV) is a potentially blinding condition characterized by the development of small, leaky, abnormal, blood vessels in the retina. This occurs as a consequence of retinal ischemia, which promotes the release of angiogenic factors such as vascular endothelial growth factor (VEGF). MicroRNAs (miRs) are non-coding RNA involved in post-transcriptional regulation of genes resulting in the blockade of their expression. MiRs are key players in a wide range of biological processes such as cell differentiation, neurogenesis, viral infection, immunity, and hypoxia. More specifically, microRNA-21 (miR-21) is upregulated in many pathological conditions including cancer, and cardiovascular disease. Previously, we have shown that microRNA-21 (miR-21) is a downstream effector of the transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) in retinal endothelial microvascular cells. Here, we will identify new therapeutic targets as well as diagnostic tools to prevent retinal neovascularization and, potentially, other ocular diseases. One well-known retinal angiostatic factor is pigmented epithelium-derived factor (PEDF). Increased miR-21 expression in the ischemic retina affects PEDF �gene� expression. Interestingly, miR-21 is known to inhibit the expression of peroxisome proliferator-activated receptor alpha (PPAR?). PPAR? is a transcription factor for PEDF; therefore, increased miR-21 level in the ischemic retina could lead to inhibition of PPR alpha expression and consequent inhibition of PEDF expression.