Role of TGFβ2 and miRNAs in optic nerve head fibrosis
| dc.contributor.author | Tovar-Vidales, Tara | |
| dc.contributor.author | Clark, Abbot | |
| dc.creator | Lopez, Navita | |
| dc.date.accessioned | 2020-12-11T14:34:07Z | |
| dc.date.available | 2020-12-11T14:34:07Z | |
| dc.date.issued | 2020 | |
| dc.description.abstract | Purpose: Glaucoma is characterised by degeneration of retinal ganglion cells (RGCs) and loss of visual function. This is associated with extracellular matrix (ECM) remodelling of the optic nerve head (ONH). The ONH provides mechanical and biochemical support to unmyelinated RGC axons as they exit the eye to form the optic nerve; thus, changes in the ONH affect the physiology of axons and may damage the visual circuitry. In glaucoma, mechanosensitive cells in the ONH respond to elevated pressure by secreting growth factors, ECM and inflammatory cytokines that damage RGCs and remodel the ONH. A key upregulated pathway in glaucoma is TGFβ2, which leads to increased expression of profibrotic genes. We hypothesised that impaired regulation of TGFβ2 and miRNAs is involved in glaucomatous remodelling of the ONH ECM. The purpose of this study was to identify cell-specific changes in glaucoma pathophysiology. Method: ONH astrocytes and lamina cribrosa (LC) were treated with TGFβ2 (5ng/ml) or vehicle and analyzed by miRNA qPCR arrays and NGS. Cells were transfected with candidate miRNA mimics, inhibitors, or non-targeting siRNA (10nM) to determine ECM expression. Results: TGFβ2 treatment decreased the expression of multiple antifibrotic miRNAs, which was associated with increased expression of several profibrotic genes including collagen I and IV and fibronectin. Overexpression of antifibrotic miRNAs including miR-29c-3p and miR-200b-3p decreased TGFβ2 induced collagen I and IV and fibronectin expression. Conclusion: TGFβ2 modulated the expression of several miRNAs to stimulate a profibrotic response; this may lead to pathogenic ONH remodelling. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12503/30139 | |
| dc.language.iso | en | |
| dc.title | Role of TGFβ2 and miRNAs in optic nerve head fibrosis | |
| dc.type | poster | |
| dc.type.material | text |