Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human lamina cribrosa cells in vitro treated with mechanical strain

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Ruaidhri Patrick Kirwan

PROVIDER: E-GEOD-3166 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Influence of cyclical mechanical strain on extracellular matrix gene expression in human lamina cribrosa cells in vitro.

Kirwan Ruaidhrí P RP Fenerty Cecilia H CH Crean John J Wordinger Robert J RJ Clark Abbot F AF O'Brien Colm J CJ

Molecular vision 20050923

<h4>Purpose</h4>The mechanical effect of raised intraocular pressure is a recognised stimulus for optic neuropathy in primary open angle glaucoma (POAG). Characteristic extracellular 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 i ...[more]

PMID: 16205625

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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.

Dataset Information

Transcription profiling of human lamina cribrosa cells in vitro treated with mechanical strain

Publications

Influence of cyclical mechanical strain on extracellular matrix gene expression in human lamina cribrosa cells in vitro.

Similar Datasets

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