miRNA Expression in DR Mechanism of action Regulation of VEGF by miRNA Pathogenic function Reference miR-377–3p Downregulation in serum exosomes Lack of it increases VEGF expression Negative regulation in serum exosomes Inhibit the development of DR [208 ] miR-15b Downregulation in serum miR-15b regulates the expression of VEGF by targeting the 3 Negative regulation in serum Inhibit the development of DR [115 ] miR-409–5p Upregulation in retinal tissues, in mRMECs, and in vitreous fluid Its overexpression increases the expression and secretion of VEGF Positive regulation in retinal tissues, in mRMECs, and in vitreous fluid Promote the development of DR [209 ] miR-203a-3p Downregulation in HRMECS Reduce the levels of VEGFA and HIF-α , PCNA, and MMPs in cells Negative regulation in HRMECS Inhibit the development of DR [91 ] miR-29b-3p Downregulation in RMECS miR-29b-3p negatively regulated the expression of angiogenic factors in RMECs Negative regulation in RMECS Inhibit the development of DR [210 ] miR-20a Downregulation in retinal tissues Upregulation of SIRT1 inhibits the development of DR via miR-20a-induced downregulation of YAP/HIF1α /VEGFA Negative regulation in retinal tissues Inhibit the development of DR [154 ] miR-152 Downregulation in hRECs and HRMECS Its overexpression can inhibit VEGF signaling Negative regulation in hRECs and HRMECS Inhibit the development of DR [211 ] miR-200b-3p Downregulation in RMECs AP1 may exert some promotive effects on the development of DR through its regulation of the MALAT1/miR-200b-3p/VEGFA axis, highlighting that YAP1 silencing may be instrumental for the therapeutic targeting of DR Negative regulation in RMECs Inhibit the development of DR [93 ] miR-141–3p Downregulation in retinal neovascularization and retinal ganglion cells (RGCs) Impede the activation of the DOK5-mediated MAPK signaling pathway Negative regulation in retinal neovascularization and retinal ganglion cells (RGCs) Inhibit the development of DR [191 ] miR-26a Downregulation in retinal tissues Reduce the levels of VEGF, IL-1β , and NF-κ B Negative regulation in retinal tissues miR-26a can protect against retinal neuronal impairment in diabetic mice by downregulating PTEN [182 ] miR-145 Downregulation in HRMECS Reduce the levels of VEGF, IL-1β , and NF-κ B Negative regulation in HRMECS Inhibition of miR-145 abolished the beneficial role of TUG1 knockdown in HG-treated HRMECS. Inhibit the development of DR [212 ] miR-23a Downregulation in blood and tear Lack of it increases VEGF expression Negative regulation in blood and tear May regulate microvascular growth at the retina via VEGF and contribute to DR progression [213 ] miR-9–3p Upregulation in Müller glia cells Mechanistically, exosomal miRNA-9–3p was transferred to retinal endothelial cells and bound to the sphingosine-1-phosphate receptor S1P1 coding sequence, which subsequently activated VEGFR2 phosphorylation and internalization in the presence or absence of exogenous VEGF-A Positive regulation in Müller glia cells S1P1 was identified as the key component of miR-9–3p to regulate abnormal angiogenesis [171 ] miR-1281 Upregulation in serum miR-1281 positively regulates VEGFA protein expression through activation of VEGFA gene transcription Positive regulation in serum Promote the expression of VEGFA [108 ] miR-223–3p Upregulation in a zebrafish model Overexpression increases VEGF levels Positive regulation in a zebrafish model miR-223–3p negatively regulates eukaryotic translation initiation factor 4E family member 3 (EIF4E3) and insulin-like growth factor 1 receptor (IGF1R) [214 ] miR-181d-5p Downregulation in HRMECS miR-181d-5p directly targeted and negatively regulated VEGFA Negative regulation in HRMECS miR-181d-5p inhibition augmented cell proliferation, migration, and angiogenesis of HRMECS caused by HG [215 ] miR-139-5p Upregulation in RMECs Targeted inhibition PTEN Positive regulation in RMECs Promotes cell migration, tube formation, and VEGF protein level [216 ]
