Inhibitory effect of miR-182-5p on retinal neovascularization by targeting angiogenin and BDNF

Retinal neovascularization (RNV) is a type of serious vision-threating disease, commonly induced by hypoxia of ischemic retinopathy, which happens in various ocular diseases including diabetic retinopathy and retinopathy of prematurity. In clinical work, anti-VEGF therapy is the preferred strategy for treating RNV. However, not all cases are sensitive to anti-VEGF injection. It is urgent and necessary to develop novel targets for inhibiting neovascularization in ocular diseases. Angiogenin (ANG) and brain-derived neurotrophic factor (BDNF) are implicated in angiogenesis, although their regulation and effects in RNV remain to be elucidated. microRNA (miRNA) is a type of small non-coding RNA, which can modulate targets by degrading transcripts or inhibiting protein translation. In the present study, miRNA-mediated modulation of ANG and BDNF was explored in an oxygen-induced retinopathy mouse model and human retinal microvascular endothelial cells (HRECs) under hypoxia. The results showed that downregulation of miR-182-5p and upregulation of ANG and BDNF were found in vivo and in vitro. Overexpression of miR-182-5p suppressed the expression of ANG and BDNF significantly in HRECs under hypoxia. In addition, knockdown of ANG and BDNF by miR-182-5p transfection significantly improved hypoxia-induced HRECs dysfunctions, including enhancing cell viability, reducing cell migration and improved tube integrity. In conclusion, miRNA-dependent regulation on ANG and BDNF indicates a critical role in hypoxia-induced retinal microvascular response. miR-182-5p-based therapy can influence the expression of ANG and BDNF, which demonstrates the potential for treating RNV diseases.