Chun Yang1, Houda Tahiri1, Chenrongrong Cai1, Muqing Gu2, Carmen Gagnon1, Pierre Hardy1. 1. Departments of Pediatrics, Physiology and Pharmacology, University of Montreal, Montreal, QC, Canada. 2. Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
Abstract
AIM: 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. microRNA-181a (miR-181a) was found highly expressed in retina and choroidal tissues. This study intends to investigate the role of miR-181a in the regulation of ocular neovascularization in different pathophysiological conditions. METHOD: We performed the RNA sequence to identify the microRNAs components of anti-angiogenic lymphocyte-derived microparticles (LMPs). The effect of miR-181a on human retinal endothelial cells proliferation was assessed in vitro. The impact of miR-181a on angiogenesis was confirmed using in vitro angiogenesis assay, ex vivo choroidal explant, and in vivo retinal neovascularization. The expression of major angiogenic factors was assessed by real-time qPCR. RESULTS: RNA sequence revealed that miR-181a is selectively enriched in LMPs. Importantly, the inhibition of miR-181a significantly abrogated the effect of LMPs on endothelial viability, but overexpression of miR-181a reduced endothelial cell viability in a dose-dependent manner. miR-181a strongly inhibited in vitro angiogenesis and ex vivo choroidal neovascularization. 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 effect, several angiogenesis-related genes were dysregulated in the miR-181a overexpressed endothelial cells. CONCLUSION: 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 neovascular diseases.
AIM: 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. microRNA-181a (miR-181a) was found highly expressed in retina and choroidal tissues. This study intends to investigate the role of miR-181a in the regulation of ocular neovascularization in different pathophysiological conditions. METHOD: We performed the RNA sequence to identify the microRNAs components of anti-angiogenic lymphocyte-derived microparticles (LMPs). The effect of miR-181a on human retinal endothelial cells proliferation was assessed in vitro. The impact of miR-181a on angiogenesis was confirmed using in vitro angiogenesis assay, ex vivo choroidal explant, and in vivo retinal neovascularization. The expression of major angiogenic factors was assessed by real-time qPCR. RESULTS: RNA sequence revealed that miR-181a is selectively enriched in LMPs. Importantly, the inhibition of miR-181a significantly abrogated the effect of LMPs on endothelial viability, but overexpression of miR-181a reduced endothelial cell viability in a dose-dependent manner. miR-181a strongly inhibited in vitro angiogenesis and ex vivo choroidal neovascularization. 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 effect, several angiogenesis-related genes were dysregulated in the miR-181a overexpressed endothelial cells. CONCLUSION: 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 neovascular diseases.