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Qinbo Zhou, William Anderson, Rafael Ufret-Vincenty, Shusheng Wang; Regulation Of Choroidal Neovascularization By MicroRNAs. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6472.
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Choroidal neovascularization (CNV) is the hallmark of "wet" age-related macular degeneration (AMD). In spite of the recent success in anti-VAGF therapy for wet AMD, limited efficacy and potential safety concern necessitate the development of additional therapeutic solutions. microRNAs (miRNAs, miRs) are small endogenous RNAs which regulate the expression of genes in multiple pathways post-transcriptionally. Our previous studies have suggested that miRNAs are key regulators of angiogenesis. We found that manipulating miRNA levels was sufficient to repress angiogenesis by in vitro and in vivo models, which have inspired us to explore miRNA function in wet AMD. We recently reported that inhibition of two miRNAs, miR-23 and miR-27, in the miR-23~27~24 families significantly represses laser-induced CNV. This project focuses on further dissecting miR-23/27/24 functional mechanisms in CNV individually and cooperatively.
In vitro cell culture model and in vivo miRNA mimics/LNA-anti-miR technologies were used to dissect the function of miR-23~27~24 family members in angiogenesis and laser-induced CNV in mouse models.
We found that, in addition to modulating angiogenic pathways, miR-23 and miR-27 also regulate inflammatory pathways involved in laser-induced CNV. Moreover, miR-24 in the family also regulates angiogenesis by in vitro models. Ongoing efforts are focused on testing the effect of a combination of miRNAs in CNV and their safety profiles on retinal cells.
miR-23~27~24 family plays a critical regulatory role in CNV. Since these miRNAs can regulate multiple pathways involved in CNV, they represent an attractive therapeutic target for treatment of wet AMD and other vascular retinopathies.
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