Molecular Mediators and Regulators of Retinal Angiogenesis

Retinal neovascularization is the major cause of vision loss that affects both adults and young children including premature babies. It has been a major pathology in several retinal diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinopathy of prematurity (ROP). Current treatment modalities such as anti-VEGF therapy, laser are not suitable for every patient and response to these therapies is highly variable. Thus, there is a need to investigate newer therapeutic targets for DR, ROP and AMD, based on a clear understanding of disease pathology and regulatory mechanisms involved.

Appropriate articles published till February 2021 were extracted from PUBMED using keywords like ocular angiogenesis, DR, ROP, AMD, miRNA, mRNA, and cirMiRNA and containvaluable information regarding the involvement of miRNA in causing neovascularization. After compiling the list of miRNA regulating mRNA expression in angiogenesis and neovascularaization, their interactions were studied using online available tool MIENTURNET (http://userver.bio.uniroma1.it/apps/mienturnet/). The pathways involved in these processes were also predicted using the same tool.

Most of the studies have explored potential targets like HIF1-α, PDGF, TGFβ, FGF, etc., for their involvement in pathological angiogenesis in different retinal diseases. The regulatory role of microRNA (miRNA) has also been explored in various retinal ocular pathologies. This review highlights regulatory mechanism of cellular and circulatory miRNAs and their interactions with the genes involved in retinal neovascularization. The role of long noncoding RNA (ncRNA) in the regulation of genes involved in different pathways is also noteworthy and discussed in this review.

This review highlights the potential regulatory mechanism/pathways involved in retinal neovascularization and its implications in retinal diseases and for identifying new drug targets.