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
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.
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.
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.
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
Project description:Compared the gene expression profiles of human vascular smooth muscle cells in response to cyclical mechanical strain over a time course of 2, 4 and 24 hours to examine temporal pattern of gene expression in response to strain.
