MicroRNA signature and function in retinal neovascularization

Abstract

Ischemic retinopathies are clinically well-defined chronic microvascular complications characterized by gradually progressive alterations in the retinal microvasculature and a compensatory aberrant neovascularization of the eye. The subsequent metabolic deficiencies result in structural and functional alterations in the retina which is highly susceptible to injurious stimuli such as diabetes, trauma, hyperoxia, inflammation, aging and dysplipidemia. Emerging evidence indicates that an effective therapy may require targeting multiple components of the angiogenic pathway. Conceptually, mircoRNA (miRNA)-based therapy provides the rationale basis for an effective antiangiogenic treatment. miRNAs are an evolutionarily conserved family of short RNAs, each regulating the expression of multiple protein-coding genes. The activity of specific miRNAs is important for vascular cell signaling and blood vessel formation and function. Recently, important progress has been made in mapping the miRNA-gene target network and miRNA-mediated gene expression control. Here we highlight the latest findings on angiogenic and antiangiogenic miRNAs and their targets as well as potential implications in ocular neovascular diseases. Emphasis is placed on how specific vascular-enriched miRNAs regulate cell responses to various cues by targeting several factors, receptors and/or signaling molecules in order to maintain either vascular function or dysfunction. Further improvement of our knowledge in not only miRNA specificity, turnover, and transport but also how miRNA sequences and functions can be altered will enhance the therapeutic utility of such molecules.

Keywords: MircoRNA; Angiogenesis; Retinal neovascularization; Vascular endothelial growth factor; Ischemia; Endothelial cell

Core tip: This review examines the critical regulatory role of microRNAs (miRNAs) in the process of normal and pathological angiogenesis and the prospects that they provide for the development of new treatments. miRNAs are both upstream and downstream of multiple growth factors in regulating endothelial proliferation, migration, and vascular patterning, processes critical for normal and abnormal formation of blood vessels. Emphasis in this review is placed on how specific vascular-enriched miRNAs regulate cell responses to various cues by targeting several factors, receptors and/or signaling molecules in order to maintain either vascular function or dysfunction.