Table 2.

Summary of miRNA treatment of DR via anti-VEGF.

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′ untranslated regions to inhibit its transcription	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-κB	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-κB	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]