Table 2.
Compiled list of all miRNAs discussed in this review listed in chronological order by the anatomic structural regions of the eye in which they were studied. The methods used to analyze the miRNAs in each study are listed in column 2. The experimental design, including sample size and grouping for each study, are listed in column 3. The conclusions of each study in context to miRNA expression or affected genes/pathways are listed in column 4. The average number of reads for each miRNA after miRNA-Seq using RNA from seven normal human TM samples are listed in column 5.
| Reference | Methods | Experimental Design |
Conclusion | Expression in HTM1 |
|---|---|---|---|---|
| AQUEOUS HUMOR | ||||
| Tanaka et al., 2014 | miRNA array (Toray Industries) | 10 control (cataract & epiretinal membrane) 10 glaucoma (1 PACG, 7 POAG, 2 PEX) |
↑ miR-1587, miR-486-3p, miR-3185, miR-940, miR-3652, miR-3135b, miR-5572, miR-4640-5p, miR-4259, miR-92a-2-5p, miR-4449 ↓ miR-4507, miR-3620-5p, miR-4484, miR-5001-5p, miR-6132, miR-6515-3p, miR-4467, miR-3663-3p, miR-187-3p, miR-4433-5p, miR-6717-5p, miR-6722-3p, miR-4725-3p, miR-1202, miR-3197, miR-4749-5p, miR-1260b, miR-4634 |
hsa-miR-486-3p (0.29); hsa-miR-940 (0.43); hsa-miR-3135b (0.57) |
| Liu et al., 2016 | Small RNA-Seq (Illumina MiSeq), ddPCR | NEIGHBORHO OD analysis: 33,480 control, 3853 POAG miRNA-Seq & ddPCR: 10 healthy donors |
↑ MIR182 point mutation = miR-182 | hsa-miR-182-5p (525.43) |
| Jayaram et al., 2017 | miRNA array (Applied Biosystems, Thermo Fisher Scientific) | 8 cataract control, 6 POAG | ↑ miR-518d, miR-143 ↓ miR-660 |
hsa-miR-143-3p (31562.00); hsa-miR-143-5p (4.86); hsa-miR-660-5p (33.14) |
| Drewry et al., 2018 | NanoString, ddPCR | NanoString: 11 cataract control, 12 POAG, 12 XFG ddPCR: 10 cataract control, 17 POAG, 14 XFG |
↑ miR-302d-3p, miR-451a, miR-122-5p, miR-3144-3p, miR-320e, miR-630 ↓ miR-125b-5p, miR-320a |
hsa-miR-125b-5p (1349.29); hsa-miR-302d-3p (0); hsa-miR-451a (13.86) |
| Liu et al., 2018 | Small RNA-Seq (Illumina) | 9 cataract control, 9 POAG | ↑ 15 miRNAs ↓ 73 miRNAs |
N/A |
| Yang et al., 2018 | Real-time RT-PCR, Luciferase reporter assay | 8 cataract control, 16 glaucoma | ↑ miR-211 = ↓ Frs2 | hsa-miR-211-3p (0); hsa-miR-211-5p (608.43) |
| Hindle et al., 2019 | Qiagen miRNA PCR Array | 3 control, 6 POAG | ↑ miR-4667-5p, miR-99b-3p, miR-637, miR-4490, miR-1253, miR-3190-3p, miR-3173-3p, miR-608, miR-4725-3p, miR-4448, miR-323b-5p, miR-4538, miR-3913-3p, miR-3159, miR-4663, miR-4767, miR-4724-5p, miR-1306-5p, miR-181b-3p, miR-433-3p | hsa-miR-99b-3p (1.29); hsa-miR-4448 (0); hsa-miR-323-5p (0); hsa-miR-3159 (0); hsa-miR-1306-5p (0.29); hsa-miR-181b-3p (0); hsa-miR-433-3p (0.57) |
| Hubens et al., 2021 | Small RNA-Seq (Illumina) | 10 cataract control, 9 POAG | ↑ miR-30a-3p, miR-143-3p, miR-211-5p, miR-221-3p ↓ miR-92a-3p, miR-451a, miR-486-5p |
hsa-miR-30a-3p (115.57); hsa-miR-143-3p (31562.00); hsa-miR-211-5p (608.43); hsa-miR-221-3p (48.43); hsa-miR-92a-3p (1258.00); hsa-miR-451a (13.86); hsa-miR-486-5p (438.00) |
| TEARS | ||||
| Tamkovich et al., 2019 | Small RNA-Seq (Illumina MiSeq) | 29 healthy control, 33 POAG | ↑ miR-146b, miR-16, miR-126 | hsa-miR-146b-3p (0.86); hsa-miR-146b-5p (27.57); hsa-miR-16-5p (505.43); hsa-miR-126-3p (153.86); hsa-miR-126-5p (2237.57) |
| Raga-Cervera et al., 2021 | Small RNA-Seq (Illumina) | 22 OHT control, 20 POAG | ↑ miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-27a-3p ↓ miR-151a-3p, miR-1307-3p |
hsa-miR-26b-5p (287.86); hsa-miR-152-3p (6.86); hsa-miR-30e-5p (25.86); hsa-miR-224-5p (0.43); hsa-miR-151a-3p (375.00); hsa-miR-1307-3p (1.43); hsa-miR-27a-3p (142.57) |
| TRABECULAR MESHWORK | ||||
| Li et al., 2009 | miRNA array (Asuragen Inc.), real-time RT-PCR, Luciferase assay | Senescent HTM cells from 3 donors and matched non-senescent controls | ↑ miR-200c, miR-182, miR-139, miR-183, miR-192 ↓ miR-15a, miR-15b, miR-16, miR-17-5p, miR-18a, miR-20a, miR-92, miR-106a, miR-106b, miR-146b, miR-195, miR-199b, miR-204, miR-342 ↑ miR-106a = ↓ p21 and ↑ cell proliferation ↑ miR-182 = ↓ RARG and ↑ SA-beta-galactosidase activity |
hsa-miR-200c-3p (202.14); hsa-miR-200c-5p (0.14); hsa-miR-182-5p (525.43); hsa-miR-139-3p (1); hsa-miR-139-5p (16.71); hsa-miR-183-5p (22.43); hsa-miR-192-5p (430.43); hsa-miR-15a-5p (3.00); hsa-miR-15b-3p (0.14); hsa-miR-15b-5p (13.43); hsa-miR-16-5p (505.43); hsa-miR-17-5p (11.14); hsa-miR-18a-3p (0); hsa-miR-18a-5p (0.29); hsa-miR-20a-3p (0.29); hsa-miR-20a-5p (13.57); hsa-miR-92a-1-5p (0.57); hsa-miR-92a-3p (1258.00); hsa-miR-92b-3p (245.43); hsa-miR-106a-5p (0.29); hsa-miR-106b-3p (2.14); hsa-miR-106b-5p (3.57); hsa-miR-146b-3p (0.86); hsa-miR-146b-5p (27.57); hsa-miR-195-3p (3.71); hsa-miR-195-5p (62.29); hsa-miR-199b-3p (94.86); hsa-miR-199b-5p (175.14); hsa-miR-204-3p (0.43); hsa-miR-204-5p (2449.00); hsa-miR-342-3p (55.71); hsa-miR-342-5p (0.29) |
| Luna et al., 2009 | Luciferase assay, real-time RT-PCR | 3 sets of miR-29b mimic or mimic control of HTM cells from one donor without eye disease | ↑ miR-29b = ↓ ECM components, BMP1, ADAM12, and NKIRAS2 | hsa-miR-29b-1-5p (0.29); hsa-miR-29b-2-5p (0.43); hsa-miR-29b-3p (26.00) |
| Li et al., 2010b | Luciferase assay, real-time RT-PCR | 3-4 replicates of HTM cells from one donor | ↑ miR-183 = ↓ ITGB1, KIF2A ↓ cell adhesion ↑ phagocytosis |
hsa-miR-183-5p (22.43) |
| Li et al., 2010a | Real-time RT-PCR | HTM cells from two donors at p15 or p4 Or HTM cells from three donors transfected with miR-146a mimic or mimic control |
↑ miR-146a, miR-192, miR-329, miR-369-5p, miR-409-5p, miR-432, miR-493, miR-495 ↓ miR-204, miR-183, miR-182, miR-155, miR-92, miR-20a, miR-20b, miR-18a, miR-17–5p, miR-106a ↑ miR-146a = ↓ CCL2, CXCL3, IL11, SLC10A3, PTGS1, IL6, GALNT10, CCL20, CXCL6, PPP2R1B, SERPINE1, HAS1, IL8, IRAK1 During senescence: ↑ IL8, PAI-1, CXCL6, CCL20, IL6, CXCL3, CCL2 ↓ HAS1, PPP2R1B |
hsa-miR-146a-5p (126.29); hsa-miR-192-5p (430.43); hsa-miR-329-3p (0.14); hsa-miR-369-5p (0.14); hsa-miR-409-5p (0.14); hsa-miR-432-5p (5.29); hsa-miR-493-3p (3.00); hsa-miR-493-5p (10.86); hsa-miR-495-3p (0.43); hsa-miR-204-3p (0.43); hsa-miR-204-5p (2449.00); hsa-miR-183-5p (22.43); miR-182-5p (525.43); hsa-miR-155-5p (15.71); hsa-miR-92a-1-5p (0.57); hsa-miR-92a-3p (1258.00); hsa-miR-92b-3p (245.43); hsa-miR-20a-3p (0.29); hsa-miR-20a-5p (13.57); hsa-miR-20b-5p (0.57); hsa-miR-18a-3p (0); hsa-miR-18a-5p (0.29); hsa-miR-17-5p (11.14); hsa-miR-106a-5p (0.29) |
| Li et al., 2011 | Real-time RT-PCR, Luciferase assay | HTM cells from 2 donors transfected with miR-204 mimic or mimic control | ↑ miR-204 = ↓ AP1S2, Bcl2l2, BIRC2, EDEM1,EZR, FZD1, M6PR, RAB22A, RAB40B, SERP1, TCF12, TCF4 ↑ miR-204 = ↑ apoptosis, cytotoxicity, accumulation of carbonylated proteins, expression of ER stress markers and ↓ inflammatory factors |
hsa-miR-204-3p (0.43); hsa-miR-204-5p (2449.00) |
| Luna et al., 2011a | Real-time RT-PCR, luciferase reporter assay | Triplicates of miR-29 mimic or mimic control of HTM cells from 3 donors without eye disease | TGF-β2 = ↓ miR-29 and miR-29 = ↓ TGF-β2 |
hsa-miR-29a-3p (152.71); hsa-miR-29a-5p (0.14); hsa-miR-29b-1-5p (0.29); hsa-miR-29b-2-5p (0.43); hsa-miR-29b-3p (26.00); hsa-miR-29c-3p (88.00); hsa-miR-29c-5p (1.29) |
| Luna et al., 2011b | Real-time RT-PCR, Luciferase reporter assay | Triplicates of miR-24 mimic or mimic control of HTM cells from 2 donors without eye disease | CMS = ↑ miR-16, miR-27a, miR-27b, miR-7, let-7f, miR-26a, miR-24 and ↑ miR-24 = ↓ FURIN |
hsa-miR-16-5p (505.43); hsa-miR-27a-3p (142.57); hsa-miR-27b-3p (4044.29); hsa-miR-7-1-3p (0.43); hsa-miR-7-5p (0); hsa-let-7f-1-3p (2.71); hsa-let-7f-2-3p (5.29); hsa-let-7f-5p (4104.29); hsa-miR-26a-1-3p (0.57); hsa-miR-26a-2-3p (1.86); hsa-miR-26a-5p (16979.29); hsa-miR-24-2-5p (0.71); hsa-miR-24-3p (28.29); hsa-miR-24-2-5p (0.71) |
| Luna et al., 2012 | Real-time RT-PCR, Luciferase reporter assay | Triplicates of miR-200c mimic or mimic control of HTM cells from 2 donors without eye disease; 7 scramble mimic rats and 7 miR-200c mimic rats | ↑ miR-200c = ↓ ETAR, LPAR1, FHOD1, ZEB1, and ZEB2 and ↑ miR-200c = ↓ IOP |
hsa-miR-200c-3p (202.14); hsa-miR-200c-5p (0.14) |
| Paylakhi et al., 2013 | Real-time RT-PCR | Triplicates of miR-204 or miR-211 mimic or mimic control of HTM cells from 2 donors | ↑ miR-204 & miR-211 = ↓ FOXC1 | hsa-miR-204-3p (0.43); hsa-miR-204-5p (2449.00); hsa-miR-211-3p (0); hsa-miR-211-5p (608.43) |
| Shen et al., 2015 | Real-time RT-PCR, Luciferase reporter assay | Triplicates of HTM cells from one donor | Oxidative stress = ↓ miR-483-3p ↑ miR-483-3p = ↓ ECM genes and Smad4 |
hsa-miR-483-3p (0.14) |
| Wang et al., 2016 | Real-time RT-PCR | Triplicates of HTM cells from one donor transfected with pre-miR-93 or miR-93 sponge | ↓ miR-93 = ↑ NFE2L2 and ↓ apoptosis | hsa-miR-93-3p (0.14); hsa-miR-93-5p (31.49) |
| Li et al., 2017 | Real-time RT-PCR, Luciferase reporter assay | Triplicates of HTM cells from 3 donor without eye disease transfected with miR-143, miR-145, or control antagomiRs 23 wild-type mice, 24 miR-143/145 DKO mice |
↑ miR-143 and miR-145 in HTM miR-143/145 deletion = ↓ IOP in mice |
hsa-miR-143-3p (31562.00); hsa-miR-143-5p (4.86); hsa-miR-145-3p (0.14); hsa-miR-145-5p (615.57) |
| Ruibin et al., 2018 | Real-time RT-PCR, Luciferase reporter assay | Triplicates of HTM cells from 2 donors without eye disease transfected with miR-1298 mimic or miR-1298 inhibitor | COS = ↓ miR-1298 ↑ miR-1298 = ↓ EIF4E3 and cytotoxicity |
hsa-miR-1298-3p (0); hsa-miR-1298-5p (0.43) |
| Wang et al., 2018 | Real-time RT-PCR | Triplicates of HTM cells from one donor transfected with miR-181a mimic or si-miR-181a | ↑ miR-181a = ↓ NF-κB and JNK signaling and apoptosis | hsa-miR-181a-2-3p (58.14); hsa-miR-181a-3p (22.43); hsa-miR-181a-5p (2803.00) |
| Wang et al., 2019 | Real-time RT-PCR, Luciferase reporter assay | Triplicates of HTM cells from one donor transfected with miR- 17- 5p inhibitor or miR- 17- 5p mimic | H2O2 exposure = ↓ miR-17-5p ↑ miR-17-5p = ↓ PTEN, Bax, Bcl-xL, and Bcl-2 expression and apoptosis |
hsa-miR-17-5p (11.14) |
| Zhao et al., 2019 | Real-time RT-PCR | Triplicates of HTM cells from one donor transfected with miR-27a inhibitor or negative control and treated with 0–5 μM of Sal | Salidroside treatment = ↑ miR-27a = ↑ PI3K/AKT and Wnt/β-catenin pathways and protective effects | hsa-miR-27a-3p (142.57); hsa-miR-27a-5p (2.71) |
| Shen et al., 2020 | Real-time RT-PCR, Luciferase reporter assay | Nine replicates of HTM cells from one donor treated with 300 μM H2O2 then transfected with miR- 200c- 3p mimic or negative control mimic | ↑ miR-200c-3p = ↓ PTEN expression and apoptosis | hsa-miR-200c-3p (202.14) |
| Youngblood et al., 2020 | NanoString, ddPCR | HTM cells from 5 donors without eye disease split into 2 groups, each with 3 stretched and 3 not stretched | CMS = ↑ hsa-miR-4286, hsa-miR-29b-3p, hsa-miR-29a-3p, hsa-miR-140-5p, hsa-miR-100-5p, hsa-miR-136-5p, hsa-miR-32-5p, hsa-miR-24-3p, hsa-miR-151a-3p, hsa-miR-27a-3p, hsa-miR-4284, hsa-miR-222-3p, hsa-miR-93-5p, hsa-miR-3615, hsa-miR-21-5p, hsa-miR-376c-3p, hsa-miR-25-3p, hsa-miR-642a-3p, hsa-miR-27b-3p, hsa-miR-34a-5p, hsa-miR-127-3p, hsa-miR-31-5p, hsa-miR-377-3p, hsa-miR-22-3p, hsa-miR-15a-5p, hsa-miR-125b-5p, hsa-miR-181a-5p, hsa-miR-99b-5p, hsa-miR-30a-5p, hsa-miR-185-5p, hsa-miR-376a-3p, hsa-miR-378i, hsa-miR-574-3p, hsa-miR-337-5p, hsa-miR-125a-5p, hsa-miR-3690, hsa-miR-191-5p, hsa-miR-190a-5p, hsa-miR-181c-5p and ↓ hsa-miR-1275, hsa-miR-187-3p, hsa-miR-1323 |
hsa-miR-29b-3p (26.00); hsa-miR-29a-3p (152.71); hsa-miR-140-5p (6.86); hsa-miR-100-5p (563.29); hsa-miR-136-5p (0.71); hsa-miR-32-5p (0.29); hsa-miR-24-3p (28.29); hsa-miR-151a-3p (375.00); hsa-miR-27a-3p (142.57); hsa-miR-222-3p (16.43); hsa-miR-93-5p (31.49); hsa-miR-3615 (0.29); hsa-miR-21-5p (1692.86); hsa-miR-376c-3p (7.43); hsa-miR-25-3p (347.29); hsa-miR-27b-3p (4044.29); hsa-miR-34a-5p (19.86); hsa-miR-127-3p (851.00); hsa-miR-31-5p (0.43); hsa-miR-377-3p (1.00); hsa-miR-22-3p (8077.29); hsa-miR-15a-5p (3.00); hsa-miR-125b-5p (1349.29); hsa-miR-181a-5p (2803.00); hsa-miR-99b-5p (869.14); hsa-miR-30a-5p (268.71); hsa-miR-185-5p (0.86); hsa-miR-376a-3p (2.29); hsa-miR-574-3p (185.00); hsa-miR-337-5p (0.14); hsa-miR-125a-5p (279.14); hsa-miR-191-5p (3311.29); hsa-miR-190a-5p (0.86); hsa-miR-187-3p (0); hsa-miR-181c-5p (155.86) |
| RETINA | ||||
| Jayaram et al., 2015 | Real-time RT-PCR | 8 glaucoma model rats, 8 control rats | In glaucomatous retina from rats: ↓ miR-181c, miR-497, miR-204, let-7a, miR-29b, miR-16, miR-106b, miR-25 ↑ miR-27a |
hsa-miR-181c-3p (0); hsa-miR-181c-5p (155.86); hsa-miR-497-3p (1.00); hsa-miR-497-5p (34.57); hsa-miR-204-3p (0.43); hsa-miR-204-5p (2449.00); hsa-let-7a-2-3p (0.57); hsa-let-7a-3p (3.14); hsa-let-7a-5p (7622.29); hsa-miR-29b-1-5p (0.29); hsa-miR-29b-2-5p (0.43); hsa-miR-29b-3p (26.00); hsa-miR-16-5p (505.43); hsa-miR-106b-3p (2.14); hsa-miR-106b-5p (3.57); hsa-miR-25-3p (347.29); hsa-miR-25-5p (0); hsa-miR-27a-3p (142.57); hsa-miR-27a-5p (2.71) |
| Gao et al., 2016 | GeneChip miRNA array (Affymetrix), Real-time RT-PCR | 30 wild-type mice, 30 OPTN (E50K) transgenic mice |
OPTN (E50K) mutation = ↑ miR-141, miR-200a, miR-200b, miR-200c, miR-429 |
hsa-miR-141-3p (37.43); hsa-miR-141-5p (11.29); hsa-miR-200a-3p (25.14); hsa-miR-200a-5p (7.29); hsa-miR-200b-3p (15.29); hsa-miR-200b-5p (2.00); hsa-miR-200c-3p (202.14); hsa-miR-200c-5p (0.14); hsa-miR-429 (18.86) |
| He et al., 2018 | RT-PCR, Luciferase reporter assay | 5 replicates of Müller cells from rat retinas transfected with miR-124, anti-miR-124, or respective controls | ↑ miR-124 = ↑ RGC axon growth | hsa-miR-124-3p (0.86); hsa-miR-124-5p (0.14) |
| Li et al., 2018 | Real-time RT-PCR, Luciferase reporter assay | 5 sets of RGCs from rat transfected with miR-93-5p mimic or negative control and treated with NMDA | ↑ miR-93-5p = ↓ RGC autophagy via ↓ PTEN | hsa-miR-93-5p (31.49) |
| Nie et al., 2018 | Real-time RT-PCR, Luciferase reporter assay | 5 sets of RGCs exposed to elevated IOP transfected with miR-149 mimic, miR-149 inhibitor, or negative controls | ↓ miR-149 = ↓ RGC apoptosis | hsa-miR-149-5p (11.43) |
| Mak et al., 2020 | miRNA array (Agilent Technologies), Real-time RT-PCR, Luciferase reporter assay | 60 AAV-miR-19a-EGFP-transduced human adult RGCs, 61 AAV-EGFP-transduced human adult RGCs and triplicates of rat RGCs transfected with miR-19a mimic or scramble |
↑ miR-19a = ↑ axon regeneration via ↓ PTEN | hsa-miR-19a-3p (3.71) |
| Ou-Yang et al., 2020 | Luciferase reporter assay | Triplicates of rabbit RGCs transfected with miR-223 mimic, inhibitor, or control | ↑ miR-223 = ↑ apoptosis via ↓ HSP-70 | hsa-miR-223-3p (3.71); hsa-miR-223-5p (0) |
| Wang et al., 2021 | Real-time RT-PCR, Luciferase reporter assay | 3 control rats, 3 AOH rats, 3 agomir negative control + AOH rats, 3 miR-93 agomir + AOH rats | ↑ miR-93 = ↓ microglia activation and RGC death via ↓ STAT3 in rats | hsa-miR-93-3p (0.14); hsa-miR-93-5p (31.49) |