{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:03:48Z","timestamp":1789826628016,"version":"4.0.1"},"reference-count":137,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fight for Sight (UK)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary open angle glaucoma (POAG), a chronic optic neuropathy, remains the leading cause of irreversible blindness worldwide. It is driven in part by the pro-fibrotic cytokine transforming growth factor beta (TGF-\u03b2) and leads to extracellular matrix remodelling at the lamina cribrosa of the optic nerve head. Despite an array of medical and surgical treatments targeting the only known modifiable risk factor, raised intraocular pressure, many patients still progress and develop significant visual field loss and eventual blindness. The search for alternative treatment strategies targeting the underlying fibrotic transformation in the optic nerve head and trabecular meshwork in glaucoma is ongoing. MicroRNAs are small non-coding RNAs known to regulate post-transcriptional gene expression. Extensive research has been undertaken to uncover the complex role of miRNAs in gene expression and miRNA dysregulation in fibrotic disease. MiR-29 is a family of miRNAs which are strongly anti-fibrotic in their effects on the TGF-\u03b2 signalling pathway and the regulation of extracellular matrix production and deposition. In this review, we discuss the anti-fibrotic effects of miR-29 and the role of miR-29 in ocular pathology and in the development of glaucomatous optic neuropathy. A better understanding of the role of miR-29 in POAG may aid in developing diagnostic and therapeutic strategies in glaucoma.<\/jats:p>","DOI":"10.3390\/ijms231810216","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T20:52:51Z","timestamp":1662497571000},"page":"10216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Role of miR-29 Family in TGF-\u03b2 Driven Fibrosis in Glaucomatous Optic Neuropathy"],"prefix":"10.3390","volume":"23","author":[{"given":"Aoife","family":"Smyth","sequence":"first","affiliation":[{"name":"UCD Clinical Research Centre, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breedge","family":"Callaghan","sequence":"additional","affiliation":[{"name":"Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1246-4166","authenticated-orcid":false,"given":"Colin E.","family":"Willoughby","sequence":"additional","affiliation":[{"name":"Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"UCD Clinical Research Centre, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/ceo.13138","article-title":"Evolution of optic nerve photography for glaucoma screening: A review","volume":"46","author":"Myers","year":"2017","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"903","DOI":"10.3109\/02713683.2013.800888","article-title":"Imaging of the Lamina Cribrosa in Glaucoma: Perspectives of Pathogenesis and Clinical Applications","volume":"38","author":"Kim","year":"2013","journal-title":"Curr. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1006\/exer.1998.0539","article-title":"Elastosis of the Lamina Cribrosa in Glaucomatous Optic Neuropathy","volume":"67","author":"Pena","year":"1998","journal-title":"Exp. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0002-9394(14)75984-7","article-title":"Changes in the Extracellular Matrix of the Human Optic Nerve Head in Primary Open-Angle Glaucoma","volume":"109","author":"Hernandez","year":"1990","journal-title":"Am. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/ICU.0000000000000354","article-title":"Lamina cribrosa in glaucoma","volume":"28","author":"Downs","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0002-9394(83)90389-6","article-title":"Morphologic Changes in the Lamina Cribrosa Correlated with Neural Loss in Open-Angle Glaucoma","volume":"95","author":"Quigley","year":"1983","journal-title":"Am. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1001\/archopht.120.6.701","article-title":"The Ocular Hypertension Treatment Study: A randomized trial determines that top-ical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma","volume":"120","author":"Kass","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/s41433-019-0687-5","article-title":"Systematic reviews and randomised controlled trials on open angle glaucoma","volume":"34","author":"Wormald","year":"2019","journal-title":"Eye"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1001\/archopht.120.10.1268","article-title":"Reduction of intraocular pressure and glaucoma progression: Results from the Early Manifest Glaucoma Trial","volume":"120","author":"Heijl","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.ajo.2013.05.027","article-title":"Lifetime Risk of Blindness in Open-Angle Glaucoma","volume":"156","author":"Peters","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","first-page":"656","article-title":"Research progress on human genes involved in the patho-genesis of glaucoma","volume":"18","author":"Wang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/wdev.86","article-title":"The TGFbeta superfamily signaling pathway","volume":"2","author":"Weiss","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1136\/bjophthalmol-2011-301132","article-title":"The role of transforming growth factor \u03b2 in glaucoma and the therapeutic implications","volume":"97","author":"Prendes","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1089\/jop.2013.0220","article-title":"The Role of TGF-\u03b22 and Bone Morphogenetic Proteins in the Trabecular Meshwork and Glaucoma","volume":"30","author":"Wordinger","year":"2014","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00441-011-1274-7","article-title":"The role of TGF-\u03b2 in the pathogenesis of primary open-angle glaucoma","volume":"347","author":"Fuchshofer","year":"2011","journal-title":"Cell Tissue Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1167\/iovs.05-1060","article-title":"TGF\u03b22-induced changes in human trabecular mesh-work: Implications for intraocular pressure","volume":"47","author":"Fleenor","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1167\/iovs.08-2632","article-title":"Cochlin Expression in Anterior Segment Organ Culture Models after TGF\u03b22 Treatment","volume":"50","author":"Bhattacharya","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1167\/iovs.10-5990","article-title":"Cytokine-Dependent ELAM-1 Induction and Concomitant Intraocular Pressure Regulation in Porcine Anterior Eye Perfusion Culture","volume":"52","author":"Birke","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","first-page":"261386","article-title":"New Therapeutic Targets for Intraocular Pressure Lowering","volume":"2013","author":"Gouveia","year":"2013","journal-title":"ISRN Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Angayarkanni, N., Coral, K., Bharathi Devi, S.R., and Saijyothi, A.V. (2016). The Biochemistry of the Eye. Pharmacology of Ocular Thera-Peutics, Adis.","DOI":"10.1007\/978-3-319-25498-2_5"},{"key":"ref_22","first-page":"76","article-title":"Differential global and extra-cellular matrix focused gene expression pat-terns between normal and glaucomatous human lamina cribrosa cells","volume":"15","author":"Kirwan","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.survophthal.2017.06.007","article-title":"Aging and ocular tissue stiffness in glaucoma","volume":"63","author":"Liu","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1089\/jop.2014.0163","article-title":"The Function of Matricellular Proteins in the Lamina Cribrosa and Trabecular Meshwork in Glaucoma","volume":"31","author":"Wallace","year":"2015","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.exer.2010.07.014","article-title":"The pathogenic role of transforming growth factor-\u03b22 in glaucomatous damage to the optic nerve head","volume":"93","author":"Fuchshofer","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/glia.20247","article-title":"Transforming growth factor-\u03b2-regulated gene transcription and protein expression in human GFAP-negative lamina cribrosa cells","volume":"52","author":"Kirwan","year":"2005","journal-title":"Glia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1101\/gr.2722704","article-title":"Identification of Mammalian microRNA Host Genes and Transcription Units","volume":"14","author":"Rodriguez","year":"2004","journal-title":"Genome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-Y","article-title":"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complemen-tarity to lin-14","volume":"75","author":"Lee","year":"1993","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0092-8674(93)90530-4","article-title":"Wightman, Ha, Ruvkun-1993-Cell-Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern. PDF","volume":"75","author":"Wightman","year":"1993","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/ng1590","article-title":"Identification of hundreds of conserved and nonconserved human microRNAs","volume":"37","author":"Bentwich","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1038\/sj.emboj.7600385","article-title":"MicroRNA genes are transcribed by RNA polymerase II","volume":"23","author":"Lee","year":"2004","journal-title":"EMBO J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature01957","article-title":"The nuclear RNase III drosha initiates microRNA processing","volume":"425","author":"Lee","year":"2003","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1126\/science.1090599","article-title":"Nuclear Export of MicroRNA Precursors","volume":"303","author":"Lund","year":"2004","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1101\/gad.927801","article-title":"Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans","volume":"15","author":"Ketting","year":"2001","journal-title":"Genes Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17897","DOI":"10.1074\/jbc.R900012200","article-title":"The RNA-induced Silencing Complex: A Versatile Gene-silencing Machine","volume":"284","author":"Pratt","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature07242","article-title":"The impact of microRNAs on protein output","volume":"455","author":"Baek","year":"2008","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1126\/science.1115079","article-title":"Inhibition of Translational Initiation by Let-7 MicroRNA in Human Cells","volume":"309","author":"Pillai","year":"2005","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/nsmb1173","article-title":"Human let-7a miRNA blocks protein production on actively translating polyribosomes","volume":"13","author":"Nottrott","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrg2936","article-title":"Gene silencing by microRNAs: Contributions of translational repression and mRNA decay","volume":"12","author":"Huntzinger","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nsmb.2931","article-title":"From guide to target: Molecular insights into eukaryotic RNA-interference machinery","volume":"22","author":"Ipsaro","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrc1840","article-title":"Oncomirs\u2014microRNAs with a role in cancer","volume":"6","author":"Slack","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/jcp.25056","article-title":"MicroRNA as Biomarkers and Diagnostics","volume":"231","author":"Wang","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_44","first-page":"161","article-title":"The role of microRNAs in human diseases","volume":"2","author":"Ardekani","year":"2010","journal-title":"Avicenna J. Med. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15004","DOI":"10.1038\/sigtrans.2015.4","article-title":"The role of MicroRNAs in human cancer","volume":"1","author":"Peng","year":"2016","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13075-016-0929-x","article-title":"MicroRNAs in fibrosis: Opportunities and challenges","volume":"18","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6156","DOI":"10.1007\/s12035-019-1500-y","article-title":"Systematic Review of miRNA as Biomarkers in Alzheimer\u2019s Disease","volume":"56","author":"Swarbrick","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Colpaert, R.M., and Calore, M. (2019). MicroRNAs in Cardiac Diseases. Cells, 8.","DOI":"10.3390\/cells8070737"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lobo, J., Gillis, A.J.M., van den Berg, A., Dorssers, L.C.J., Belge, G., Dieckmann, K.-P., Roest, H.P., Van Der Laan, L.J.W., Gietema, J., and Hamilton, R.J. (2019). Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor in Vitro, in Vivo and Patient-Derived Data. Cells, 8.","DOI":"10.3390\/cells8121637"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9564","DOI":"10.1038\/s41598-022-13573-8","article-title":"Genome-wide tran-scriptome profiling of human trabecular meshwork cells treated with TGF-\u03b22","volume":"12","author":"Callaghan","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19024","DOI":"10.1038\/s41598-021-98278-0","article-title":"Profiles of microRNA in aqueous humor of normal tension glauco-ma patients using RNA sequencing","volume":"11","author":"Seong","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lopez, N., Rangan, R., Clark, A., and Tovar-Vidales, T. (2021). Mirna Expression in Glaucomatous and TGF\u03b22 Treated Lamina Cribrosa Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126178"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kang, H. (2017). Role of MicroRNAs in TGF-\u03b2 Signaling Pathway-Mediated Pulmonary Fibrosis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122527"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Suzuki, H.I. (2018). MicroRNA control of TGF-\u03b2 signaling. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071901"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"a022137","DOI":"10.1101\/cshperspect.a022137","article-title":"Signaling Cross Talk between TGF-\u03b2\/Smad and Other Signaling Pathways","volume":"9","author":"Luo","year":"2016","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-\u03b2: The master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.4103\/0366-6999.190677","article-title":"Regulatory Mechanisms of the Molecular Pathways in Fibrosis Induced by MicroRNAs","volume":"129","author":"Yang","year":"2016","journal-title":"Chin. Med. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature07086","article-title":"SMAD proteins control DROSHA-mediated microRNA maturation","volume":"454","author":"Hilyard","year":"2008","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.tips.2012.04.003","article-title":"Crosstalk between TGF-\u03b2 signaling and the microRNA machinery","volume":"33","author":"Butz","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1478-3231.2005.01192.x","article-title":"Therapeutic strategies against TGF-\u03b2 signaling pathway in hepatic fibrosis","volume":"26","author":"Liu","year":"2005","journal-title":"Liver Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1111\/j.1524-475X.2007.00226.x","article-title":"TGF-\u03b2\u2013induced fibrosis and SMAD signaling: Oligo decoys as natural therapeutics for inhibition of tissue fibrosis and scarring","volume":"15","author":"Cutroneo","year":"2007","journal-title":"Wound Repair Regen."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhang, B., Zhou, M., Li, C., Zhou, J., Li, H., Zhu, D., Wang, Z., Chen, A., and Zhao, Q. (2014). MicroRNA-92a inhibition attenuates hypox-ia\/reoxygenation-induced myocardiocyte apoptosis by targeting Smad7. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100298"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/j.ajpath.2013.08.027","article-title":"Canonical transforming growth factor-\u03b2 signaling regulates disintegrin metal-loprotease expression in experimental renal fibrosis via miR-29","volume":"183","author":"Ramdas","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1042\/BSR20201545","article-title":"miR-200-3p suppresses cell proliferation and reduces apoptosis in diabetic retinopathy via blocking the TGF-\u03b22\/Smad pathway","volume":"40","author":"Xue","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.omtn.2017.02.008","article-title":"Transcriptome-wide Investigation of mRNA\/circRNA in miR-184 and Its r.57c > u Mutant Type Treatment of Human Lens Epithelial Cells","volume":"7","author":"Luo","year":"2017","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3567","DOI":"10.1167\/iovs.10-6448","article-title":"Cross-talk between miR-29 and Transforming Growth Factor-Betas in Trabecular Meshwork Cells","volume":"52","author":"Luna","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"108197","DOI":"10.1016\/j.exer.2020.108197","article-title":"miR-21-5p: A viable therapeutic strategy for regulating intraocular pressure","volume":"200","author":"Tan","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1167\/iovs.16-19155","article-title":"miRNA Profile in Three Different Normal Human Ocular Tissues by miRNA-Seq","volume":"57","author":"Drewry","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.omto.2018.12.011","article-title":"A Systematic Review of miR-29 in Cancer","volume":"12","author":"Kwon","year":"2018","journal-title":"Mol. Ther.-Oncolytics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1261\/rna.068692.118","article-title":"Post-transcriptional control of miRNA biogenesis","volume":"25","author":"Michlewski","year":"2018","journal-title":"RNA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1152\/physiolgenomics.00141.2011","article-title":"The miR-29 family: Genomics, cell biology, and relevance to renal and cardio-vascular injury","volume":"44","author":"Kriegel","year":"2012","journal-title":"Physiol. Genom."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1681\/ASN.2010121308","article-title":"TGF-\u03b2\/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29","volume":"22","author":"Qin","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/ng.2007.30","article-title":"Widespread mi-croRNA repression by Myc contributes to tumorigenesis","volume":"40","author":"Chang","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/jcb.22630","article-title":"Transcriptional suppression of mir-29b-1\/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB","volume":"110","author":"Mott","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_75","first-page":"915","article-title":"Discovery of recurrent t (6; 7)(p25. 3; q32. 3) translocations in ALK-negative anaplastic large cell lymphomas by mas-sively parallel genomic sequencing","volume":"117","author":"Feldman","year":"2011","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1161\/HYPERTENSIONAHA.109.144428","article-title":"Renal medullary microRNAs in Dahl salt-sensitive rats: miR-29b regulates several collagens and related genes","volume":"55","author":"Liu","year":"2010","journal-title":"Hypertension"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1126\/science.1136235","article-title":"A Hexanucleotide Element Directs MicroRNA Nuclear Import","volume":"315","author":"Hwang","year":"2007","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/leu.2014.279","article-title":"MiR-29b replacement inhibits proteasomes and disrupts aggresome+autophagosome formation to enhance the antimyeloma benefit of bortezomib","volume":"29","author":"Jagannathan","year":"2014","journal-title":"Leukemia"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Liao, J.-Y., Ma, L.-M., Guo, Y.-H., Zhang, Y.-C., Zhou, H., Shao, P., Chen, Y.-Q., and Qu, L.-H. (2010). Deep Sequencing of Human Nuclear and Cytoplasmic Small RNAs Reveals an Unexpectedly Complex Subcellular Distribution of miRNAs and tRNA 3\u2032 Trailers. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010563"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4387","DOI":"10.1093\/nar\/gkr020","article-title":"Uracils at nucleotide position 9\u201311 are required for the rapid turnover of miR-29 family","volume":"39","author":"Zhang","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1101\/gad.1975411","article-title":"miR-29b is activated during neuronal maturation and targets BH3-only genes to restrict apoptosis","volume":"25","author":"Kole","year":"2011","journal-title":"Genes Dev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e668","DOI":"10.1038\/cddis.2013.184","article-title":"miR-29 targets Akt3 to reduce proliferation and facilitate differentiation of myoblasts in skeletal muscle development","volume":"4","author":"Wei","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s13238-016-0277-2","article-title":"MiR-29b suppresses the proliferation and migration of osteosarcoma cells by targeting CDK6","volume":"7","author":"Zhu","year":"2016","journal-title":"Protein Cell"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Cushing, L., Costinean, S., Xu, W., Jiang, Z., Madden, L., Kuang, P., Huang, J., Weisman, A., Hata, A., and Croce, C.M. (2015). Disruption of miR-29 Leads to Aberrant Differentiation of Smooth Muscle Cells Selectively Associated with Distal Lung Vasculature. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005238"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ccr.2006.01.025","article-title":"Unique microRNA molecular profiles in lung cancer diagnosis and prognosis","volume":"9","author":"Yanaihara","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1073\/pnas.0511155103","article-title":"The colorectal microRNAome","volume":"103","author":"Cummins","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","first-page":"836","article-title":"Effects of MicroRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma","volume":"51","author":"Xiong","year":"2010","journal-title":"Hepatology"},{"key":"ref_88","first-page":"5331","article-title":"MicroRNA 29b functions in acute myeloid leukemia","volume":"114","author":"Garzon","year":"2009","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/embor.2009.9","article-title":"miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis","volume":"10","author":"Gebeshuber","year":"2009","journal-title":"EMBO Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"15676","DOI":"10.1074\/jbc.M809787200","article-title":"Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation","volume":"284","author":"Li","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"5874","DOI":"10.1073\/pnas.0801130105","article-title":"Mi-croRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix pro-teins","volume":"105","author":"Sengupta","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1139\/bcb-2014-0095","article-title":"The role of miR-29 in pulmonary fibrosis","volume":"93","author":"Cushing","year":"2015","journal-title":"Biochem. Cell Biol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Ciechomska, M., O\u2019Reilly, S., Suwara, M., Bogunia-Kubik, K., and van Laar, J.M. (2014). MiR-29a reduces TIMP-1 production by dermal fibro-blasts via targeting TGF-\u03b2 activated kinase 1 binding protein 1, implications for systemic sclerosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115596"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/hep.23922","article-title":"Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis","volume":"53","author":"Roderburg","year":"2011","journal-title":"Hepatology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"13027","DOI":"10.1073\/pnas.0805038105","article-title":"Dysregulation of mi-croRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis","volume":"105","author":"Sutherland","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1038\/mt.2012.36","article-title":"miR-29 Inhibits Bleomycin-induced Pulmonary Fibrosis in Mice","volume":"20","author":"Xiao","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhou, L., Wang, L., Lu, L., Jiang, P., Sun, H., and Wang, H. (2012). Inhibition of miR-29 by TGF-beta-Smad3 signaling through dual mecha-nisms promotes transdifferentiation of mouse myoblasts into myofibroblasts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033766"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Pandit, K., and Kaminski, N. (2017). MicroRNAs in Idiopathic Pulmonary Fibrosis. Transl. Res., 179\u2013202.","DOI":"10.1016\/B978-0-12-800553-8.00007-X"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1165\/rcmb.2010-0323OC","article-title":"miR-29 Is a Major Regulator of Genes Associated with Pulmonary Fibrosis","volume":"45","author":"Cushing","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/jcb.24474","article-title":"MiR-29 mediates TGF\u03b21-induced extracellular matrix synthesis through activation of PI3K-AKT pathway in human lung fibroblasts","volume":"114","author":"Yang","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bbrc.2011.07.041","article-title":"Suppression of hepatic stellate cell activation by microRNA-29b","volume":"412","author":"Sekiya","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.bbrc.2009.11.056","article-title":"Suppression of type I collagen production by mi-croRNA-29b in cultured human stellate cells","volume":"391","author":"Ogawa","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.bbrc.2014.03.037","article-title":"MiR-29b inhibits collagen maturation in hepatic stel-late cells through down-regulating the expression of HSP47 and lysyl oxidase","volume":"446","author":"Zhang","year":"2014","journal-title":"Biochem. Biophys. Res. Com-Munications"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"18255","DOI":"10.1073\/pnas.0608791103","article-title":"A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure","volume":"103","author":"Sutherland","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1161\/CIRCULATIONAHA.112.001207","article-title":"MicroRNA29: A mechanistic contributor and potential biomarker in atrial fibrillation","volume":"127","author":"Dawson","year":"2013","journal-title":"Circulation"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/cvr\/cvq053","article-title":"Downregulation of microRNA-29 by antisense inhibitors and a PPAR-\u03b3 agonist protects against myocardial ischaemia\u2013reperfusion injury","volume":"87","author":"Ye","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6133","DOI":"10.1038\/sj.onc.1210436","article-title":"mir-29 regulates Mcl-1 protein expression and apoptosis","volume":"26","author":"Mott","year":"2007","journal-title":"Oncogene"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nsmb.1533","article-title":"miR-29 miRNAs activate p53 by targeting p85\u03b1 and CDC42","volume":"16","author":"Park","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1582-4934.2008.00510.x","article-title":"MicroRNA and cancer\u2013focus on apoptosis","volume":"13","author":"Wang","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1038\/nm1320","article-title":"The antioxidant function of the p53 tumor suppressor","volume":"11","author":"Sablina","year":"2005","journal-title":"Nat. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/mt.2013.235","article-title":"MicroRNA-29b Inhibits Diabetic Nephropathy in db\/db Mice","volume":"22","author":"Chen","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1002\/art.27443","article-title":"MicroRNA-29, a key regulator of collagen expression in systemic sclerosis","volume":"62","author":"Maurer","year":"2010","journal-title":"Arthritis Rheumatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s10875-011-9647-y","article-title":"MicroRNA Expression Abnormalities in Limited Cutaneous Scleroderma and Diffuse Cutaneous Scleroderma","volume":"32","author":"Zhu","year":"2012","journal-title":"J. Clin. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/ced.12734","article-title":"A novel regulatory function for miR-29a in keloid fibrogenesis","volume":"41","author":"Zhang","year":"2015","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"BSR20171157","DOI":"10.1042\/BSR20171157","article-title":"Roles of miRNAs and long noncoding RNAs in the progression of diabetic retinopathy","volume":"37","author":"Gong","year":"2017","journal-title":"Biosci. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1186\/s12864-015-1772-1","article-title":"Integrated analyses of zebrafish miRNA and mRNA expression profiles identify miR-29b and miR-223 as potential regulators of optic nerve regeneration","volume":"16","author":"Carter","year":"2015","journal-title":"BMC Genom."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1167\/iovs.14-14154","article-title":"Extracellular Matrix Alterations in Late-Onset Fuchs\u2019 Corneal Dystrophy","volume":"55","author":"Weller","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1097\/ICO.0000000000000954","article-title":"MicroRNA-29b over-expression decreases extracellular matrix mRNA and protein production in human corneal endothelial cells","volume":"35","author":"Toyono","year":"2016","journal-title":"Cornea"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s00417-020-04634-7","article-title":"Genipin inhibits the scleral expression of miR-29 and MMP2 and pro-motes COL1A1 expression in myopic eyes of guinea pigs","volume":"258","author":"Wang","year":"2020","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s11626-015-9990-z","article-title":"MicroRNA-29 regulates high-glucose-induced apoptosis in hu-man retinal pigment epithelial cells through PTEN","volume":"52","author":"Lin","year":"2016","journal-title":"Vitr. Cell. Dev. Biol.-Anim."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.1167\/iovs.10-6165","article-title":"Coordinated regulation of extracellular matrix synthesis by the microRNA-29 family in the trabecular meshwork","volume":"52","author":"Villarreal","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.exer.2012.10.016","article-title":"MicroRNA in aqueous humor from patients with cataract","volume":"108","author":"Dunmire","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1167\/iovs.15-17828","article-title":"MicroRNA Profiling in Aqueous Humor of Individual Human Eyes by Next-Generation Sequencing","volume":"57","author":"Wecker","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_124","first-page":"4799","article-title":"TGF-\u03b22 stimulates Tenon\u2019s capsule fibroblast proliferation in patients with glaucoma via suppres-sion of miR-29b expression regulated by Nrf2","volume":"8","author":"Ran","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1167\/iovs.11-8670","article-title":"Suppression of Type I Collagen Expression by miR-29b via PI3K, Akt, and Sp1 Pathway in Human Tenon\u2019s Fibroblasts","volume":"53","author":"Li","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"7971","DOI":"10.1167\/iovs.15-18088","article-title":"MicroRNA Expression in the Glaucomatous Retina","volume":"56","author":"Jayaram","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3892\/ijmm.2021.4934","article-title":"Silencing microRNA-29b-3p expression protects human trabecular meshwork cells against oxidative injury via upregulation of RNF138 to activate the ERK pathway","volume":"47","author":"Liu","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_128","first-page":"2488","article-title":"Role of miR-29b on the regulation of the extracellular matrix in human trabec-ular meshwork cells under chronic oxidative stress","volume":"15","author":"Luna","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"7433","DOI":"10.1167\/iovs.13-12652","article-title":"Canonical wnt signaling regulates extracellular matrix expres-sion in the trabecular meshwork","volume":"55","author":"Villarreal","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.exer.2016.04.007","article-title":"Crosstalk between TGF\u03b2 and Wnt signaling pathways in the human trabecular meshwork","volume":"148","author":"Webber","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/iovs.61.5.2","article-title":"Expression of mRNAs, miRNAs, and lncRNAs in Human Trabecular Meshwork Cells Upon Mechanical Stretch","volume":"61","author":"Youngblood","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"6019","DOI":"10.1167\/iovs.15-16558","article-title":"Suppression of Type I Collagen Expression by miR-29b Via PI3K, Akt, and Sp1 Pathway, Part II: An in Vivo Investigation","volume":"56","author":"Yu","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_133","first-page":"5316","article-title":"Inhibition of ocular fibrosis with a miR-29b mimic","volume":"59","author":"Propp","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.bbamcr.2010.06.013","article-title":"MicroRNAs: Synthesis, mechanism, function, and recent clinical trials","volume":"1803","author":"Wahid","year":"2010","journal-title":"Biochim. Et Biophys. Acta Mol. Cell Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.4155\/fmc.14.116","article-title":"miRNA-based therapies: Strategies and delivery platforms for oligonucleotide and non-oligonucleotide agents","volume":"6","author":"Baumann","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40291-016-0234-z","article-title":"An Eye on Age-Related Macular Degeneration: The Role of MicroRNAs in Disease Pathology","volume":"21","author":"Berber","year":"2016","journal-title":"Mol. Diagn. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12886-022-02368-0","article-title":"Identification of the potential biological target molecules related to primary open-angle glaucoma","volume":"22","author":"Li","year":"2022","journal-title":"BMC Ophthalmol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10216\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:24:04Z","timestamp":1760142244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,6]]},"references-count":137,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810216"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810216","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,6]]}}}