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Pierre Hardy, ChenRongRong Cai, Chun Yang, Stephane Croteau; microRNA-181a exhibits inhibitory effect on ocular neovascularization. Invest. Ophthalmol. Vis. Sci. 2018;59(9):222.
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Excess angiogenesis or neovascularization plays a key role in the pathophysiology of several ocular diseases such as retinopathy of prematurity, diabetic retinopathy and exudative age-related macular degeneration. The microRNA-181a (miR-181a) is highly expressed in ocular tissues such as retina and choroid. This study was designed to investigate the role of miR-181a in the regulation of ocular neovascularization in different pathophysiological conditions.
The miR-181a was overexpressed by transfection of miR-181a-5p mimic or transduction by lentiviral-GFP-miR-181a-5p. The effect of miR-181a on human retinal endothelial cell proliferation was assessed in vitro. The impact of miR-181a on angiogenesis was confirmed using ex vivo choroidal explant and in vivo retinal neovascularization. The expression of major angiogenic factors was assessed by real-time qPCR and western blot.
The overexpression of miR-181a reduced human retinal endothelial cell proliferation in a dose-dependent manner. MiR-181a strongly inhibited ex vivo human choroidal neovascularization with a reduction of 84% compared to the control. The strong anti-angiogenic effect of miR-181a was also displayed on the retinal neovascularization of the in vivo mouse model of oxygen-induced retinopathy. In keeping with its suppressive effect, the expressions of proangiogenic factors B-cell lymphoma 2 (BCL2, a direct target of miR-181a) and VEGF were downregulated in the miR-181a overexpressed retinal endothelial cells.
These data may open unexpected avenues for the development of miR-181a as a novel therapeutic strategy that would be particularly useful and relevant for the treatment of ocular neovascular diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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