MiRNA Expression in Glaucomatous and TGFb2 Treated Lamina Cribrosa cells
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ABSTRACT:
PROVIDER: PRJNA737444 | ENA |
REPOSITORIES: ENA
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Project description:We determined the differential expression of miRNAs that target extracellular matrix mRNAs in glauocmatous and TGFb2 treated lamina cribrosa cells compared to normal lamina cribrosa cells.
2021-06-15 | GSE178137 | GEO
Project description:Primary open angle glaucoma (POAG) is a progressive optic neuropathy, which is a major cause of worldwide visual impairment and blindness. Pathological hallmarks of the glaucomatous optic nerve head include retinal ganglion cell axon loss and extracellular matrix (ECM) remodeling of the lamina cribrosa layer. TGF-beta is an important pro-fibrotic modulator of ECM metabolism, whose levels are elevated in human POAG lamina cribrosa tissue compared with non-glaucomatous controls. We treated human lamina cribrosa (LC) cells with TGF-beta1 (10ng/ml) for 24 hours in order to examine differential gene expression patterns in repsonse to this cytokine. In particular we focused on ECM and fibrotic genes. We found that TGF-beta1 induces expression and release of ECM components in LC cells, which may be important in regulating matrix remodeling in the lamina cribrosa. In disease states such as POAG, the LC cell may represent an important pro-fibrotic cell type and an attractive target for novel therapeutic strategies.
2008-06-12 | E-GEOD-2705 | biostudies-arrayexpress
Project description:Primary open angle glaucoma (POAG) is a progressive optic neuropathy, which is a major cause of worldwide visual impairment and blindness. Pathological hallmarks of the glaucomatous optic nerve head include retinal ganglion cell axon loss and extracellular matrix (ECM) remodeling of the lamina cribrosa layer. TGF-beta is an important pro-fibrotic modulator of ECM metabolism, whose levels are elevated in human POAG lamina cribrosa tissue compared with non-glaucomatous controls. We treated human lamina cribrosa (LC) cells with TGF-beta1 (10ng/ml) for 24 hours in order to examine differential gene expression patterns in repsonse to this cytokine. In particular we focused on ECM and fibrotic genes. We found that TGF-beta1 induces expression and release of ECM components in LC cells, which may be important in regulating matrix remodeling in the lamina cribrosa. In disease states such as POAG, the LC cell may represent an important pro-fibrotic cell type and an attractive target for novel therapeutic strategies. Keywords: other
2005-08-05 | GSE2705 | GEO
Project description:Purpose: Marked extracellular matrix (ECM) remodeling occurs in the human optic nerve head in primary open angle glaucoma (POAG). The glial fibrillary acid protein (GFAP) negative lamina cribrosa cell may play an important role in this remodeling process. The authors report the first study of global and ECM-focused gene transcription differentials between GFAP-negative negative lamina cribrosa (LC) cells from normal and POAG human donors. Methods: GFAP-negative LC cell lines were generated from the optic nerve tissue of three normal (n=3) and three POAG (n=3) human donors. Using Affymetrix U133A arrays the transcriptional profile between the normal and diseased groups were compared. Bioinformatic analysis was carried out using robust multichip average (RMA Express) and EASE/David. Real time TaqMan PCR and immunohistochemistry analyses were performed to validate the microarray data. Results: 285 genes were up regulated by greater than 1.5 fold and 413 were down regulated by greater than 1.5 fold in the POAG LC cells versus normal controls. Upregulated genes in POAG LC cells included, SPARC, periostin, thrombospondin, CRTL-1, CTGF and collagen types I, III, V and VIII. Downregulated ECM genes in POAG included MMP-1, fibulin, decorin and tenacsin XB. All TaqMan PCR validation assays were significant (*p<0.05) and consistent with the array data. Immunohistochemistry of one target (periostin) confirmed its differential expression at the protein level in POAG optic nerve head tissue compared with non-glaucomatous controls. Functional annotation and over-representation analysis identified ECM genes as a statistically over-represented class of genes in POAG LC cells compared with normal LC cells. Conclusions: This study reports for the first time that POAG LC cells in-vitro demonstrate up regulated ECM and pro-fibrotic gene expression compared with normal LC cells. This may be a pathological characteristic of this cell type in POAG in-vivo. We believe that the LC cell may be a pivotal regulator of optic nerve head ECM remodeling and an attractive target for future therapeutic strategies in POAG.
2009-01-06 | GSE13534 | GEO
Project description:The mechanical effect of raised intraocular pressure is a recognised stimulus for optic neuropathy in primary open angle glaucoma (POAG). Characteristic extra-cellular matrix (ECM) remodelling accompanies axonal damage in the lamina cribrosa (LC) of the optic nerve head in POAG. Glial cells in the lamina cribrosa may play a role in this process but the precise cellular responses to mechanical forces in this region are unknown. The authors examined global gene expression profiles in lamina cribrosa cells exposed to cyclical mechanical stretch, with an emphasis on ECM genes. Experiment Overall Design: n=3 stretch and static control experiments. Experiment Overall Design: RNA pooled from each experiment and hybridised to individual experiment and control arrays.
2008-06-12 | E-GEOD-3166 | biostudies-arrayexpress
Project description:The mechanical effect of raised intraocular pressure is a recognised stimulus for optic neuropathy in primary open angle glaucoma (POAG). Characteristic extra-cellular matrix (ECM) remodelling accompanies axonal damage in the lamina cribrosa (LC) of the optic nerve head in POAG. Glial cells in the lamina cribrosa may play a role in this process but the precise cellular responses to mechanical forces in this region are unknown. The authors examined global gene expression profiles in lamina cribrosa cells exposed to cyclical mechanical stretch, with an emphasis on ECM genes. Keywords: microarray, ECM, glaucoma, mechanical stretch, lamina cribrosa
2005-08-21 | GSE3166 | GEO
Project description:Glaucoma is a group of optic neuropathies that leads to irreversible vision loss. The optic nerve head (ONH) is the site of initial optic nerve damage in glaucoma. ONH-derived lamina cribrosa (LC) cells synthesize extracellular matrix (ECM) proteins; however, these cells are adversely affected in glaucoma and cause detrimental changes to the ONH. LC cells respond to mechanical strain by increasing the profibrotic cytokine transforming growth factor-beta 2 (TGFβ2) and ECM proteins. Moreover, microRNAs (miRNAs or miR) regulate ECM gene expression in different fibrotic diseases, including glaucoma. A delicate homeostatic balance between profibrotic and anti-fibrotic miRNAs may contribute to the remodeling of ONH. This study aimed to determine whether modulation of miRNAs alters the expression of ECM in human LC cells. Primary human normal and glaucoma LC cells were grown to confluency and treated with or without TGFβ2 for 24 h. Differences in expression of miRNAs were analyzed using miRNA qPCR arrays. miRNA PCR arrays showed that the miR-29 family was significantly decreased in glaucomatous LC cell strains compared to age-matched controls. TGFβ2 treatment downregulated the expression of multiple miRNAs, including miR-29c-3p, compared to controls in LC cells. LC cells transfected with miR-29c-3p mimics or inhibitors modulated collagen expression.
| S-EPMC8229860 | biostudies-literature
Project description:Comparison between human normal and glaucomatous lamina cribrosa cells
| PRJNA110087 | ENA
Project description:The lack of neuroprotective treatments for retinal ganglion cells (RGCs) and optic nerve (ON) is a central challenge for glaucoma management. Emerging evidence suggests that redox factor NAD+ decline is a hallmark of aging and neurodegenerative diseases including glaucoma. Supplementation with NAD+ precursors and overexpression of the nicotinamide mononucleotide adenylyltransferase (NMNAT), the key enzyme involved in the NAD+ biosynthetic process, have significant neuroprotection effect on glaucoma. Among the three NMNAT isoforms, only NMNAT2 is enriched in neurons, especially in axons, however, its role in glaucoma is not well studied. Here we present the expression levels of the enzymes that involved in NAD+ metabolism in both naïve and glaucomatous mouse RGCs. Intriguingly, NMNAT2 is the dominant form of NMNATs in RGCs and only its mRNA level, but not NMNAT1 or NMNAT3, is significant decreased in glaucomatous RGCs. We then demonstrated proof-of-principal gene therapy strategy of restoring RGC-specific NMNAT2 and NAD+ levels by AAV2-mediated RGC-specific promoter mSncg-driven long half-life NMNAT2 mutant. This gene therapy strategy is further tested in two optic neuropathy models, traumatic ON crush model and ocular hypertension glaucoma model. RGC-specific NMNAT2 overexpression significantly promotes RGC somata and axons survival and preserves visual function in both models. Our studies suggest that the weaking of NMNAT2 expression in glaucomatous RGCs contributes to detrimental NAD+ decline and that modulating RGC intrinsic NMNAT2 level by AAV2-mSncg vector is a potent gene therapy for glaucomatous neuroprotection.
2021-08-22 | GSE182483 | GEO
Project description:Epigenetic activation of an enhancer for TGFB2 locks SSc patient fibroblasts into a pro-fibrotic synthetic state through mechanisms dependent on NF-kB and BRD4.
2019-05-21 | GSE130313 | GEO