Table 3. Circulatory miRNA biomarkers for DR.
| miRNA | Tissue | Targets | Action | Reference |
|---|---|---|---|---|
| miR-210 | Serum | Vascular endothelial cell proliferation | Upregulation Biomarker for PDR vs. NPDR | (39) |
| miR-320, miR-320a, miR-320b | Hu Aqueous, Vitreous, plasma | Silencing neuropilin 1, VEGF co-receptor; insulin–PI3K signaling pathways, T1DM, thrombospondin-1 | Regulates angiogenesis | (40-43) |
| miR-27b, miR-27a | Serum, vitreous | T1DM, thrombospondin-1 | Regulates angiogenesis | (40,42,44,45) |
| miR-221 | Plasma | Macrovascular complications associated with T2DM | Biomarker for PDR | (45-49) |
| Let-7a, Let-7b, Let-7c | Serum, Aqueous, vitreous | Late-stage and early-stage T2DM-DR, regulates metabolism of glucose | Regulates angiogenesis | (41,45,50,51) |
| miR-151 | Serum | Late-stage and early-stage T2DM-DR | Biomarker | (50) |
| miR-16 | Hu vitreous, aqueous,HRECs | Rho protein signal transduction, TNFα, neurotransmitter uptake, and histone lysine methylation | miR-16 decreased TNFα and HRECs and thus prevented hyperglycemia-induced apoptosis | (41,45,52) |
| miR-92 | Hu vitreous | Modulating core circadian genes involved in CD34+ progenitor differentiation, Per2 gene | Maintains CD34+ cells, reduction of miR-92a in DR | (41) |
| miR-423-5p | Hu vitreous | C20orf27, FKBP4, GDF11, HNRNPUL1, MYBL2, NACC1, PA2G4, PLCB1, SRM | gene silencing by miRNA | (42) |
| miR-93 | Hu aqueous, vitreous | Rho protein signal transduction, TNFAIP1, PLEKHG6 | Reduction in OIR, PDR | (44,52) |
| miR-184 | Hu aqueous, PDR, retina with ischemia-induced neovascularization | canonical Wnt signaling through the regulation of frizzled-7 expression | Biomarker, abundant expression in PDR, cataract | (52) |
| miR-150-5p | Hu aqueous, vitreous, PDR, plasma | CXCR4, DLL4, and FZD4 | Suppressing the expression of angiogenic regulators | (44,52) |
DR, diabetic retinopathy; PDR, proliferative diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; miR, microRNA; let, lethal; Hu, human; HREC, human retinal endothelial cells; VEGF, vascular endothelial growth factor; PI3K, Phosphatidylinositol 3-kinase; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; Rho protein, RNA-binding termination factor; TNF alpha, Tumor Necrosis Factor alpha; CD34+, marker of haemopoietic stem cells; Per2, Period Circadian Regulator 2; C20orf27, Hypothetical Protein LOC54976; FKBP4, a member of the immunophilin protein family; GDF11, growth differentiation factor 11; HNRNPUL1, heterogeneous nuclear ribonucleoprotein 1; MYBL2, MYB Proto-Oncogene Like 2; NACC1, Nucleus Accumbens Associated 1; PA2G4, proliferation-associated protein 2G4, also known as ErbB3-binding protein 1 (EBP1); PLCB1, Phospholipase C Beta 1; SRM, Rho, protein signal transduction; TNFAIP1, TNFα induced protein 1; PLEKHG6, Pleckstrin Homology And RhoGEF Domain Containing G6; Wnt, Wingless-related integration site; Frizzled-7; CXCR4, C-X-C chemokine receptor type 4; DLL4, Delta Like Canonical Notch Ligand 4; FZD4, Frizzled-4; OIR, oxygen-induced retinopathy.