The Role of miR-29 Family in TGF-β Driven Fibrosis in Glaucomatous Optic Neuropathy

Abstract

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-β) 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-β 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.

Detection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in ovarian cancer

“…When incorporating only protein-coding isoforms and removing the truncated isoforms from the analysis, the gene expression fold-change increased from 9 to 62-folds (Pcorr=3.15x10 -183 ). This overexpression of canonical COL1A1 in the TME can be explained by the absence of miR-29 silencing, as previously described 50 . The miR-29 family is known to be an EMT inhibitor 50 .…”

“…This overexpression of canonical COL1A1 in the TME can be explained by the absence of miR-29 silencing, as previously described 50 . The miR-29 family is known to be an EMT inhibitor 50 . Its silencing through the TGFβ pathway correlates with the upregulation of ECM-encoding genes, including multiple collagens, as reported in the present study.…”

“…The miR-29 family is known to be an EMT inhibitor 50 . Its silencing through the TGFβ pathway correlates with the upregulation of ECM-encoding genes, including multiple collagens, as reported in the present study.…”

Optic Neuropathies: Current and Future Strategies for Optic Nerve Protection and Repair

“…MiR-29 is a family of miRNAs which are strongly anti-fibrotic in their effects on the TGF-β signaling pathway and the regulation of extracellular matrix production and deposition. In their review, Smyth et al [ 6 ] 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 for patients with this common optic neuropathy.…”

Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?

“…Consistent with previous studies, our findings also demonstrated that miR-29c targets collagen gene expression in the retina. The expression of the miR-29 family was reported to significantly decrease in the ECs of patients suffering from Fuchs endothelial corneal dystrophy (FECD) [183]. Thus, overexpression of miR-29b and miR-29c resulted in a considerable downregulation of several ECM genes such as COL1A1, COL4A1, and LAMC1 in corneal EC.…”