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R. P. Kirwan, M. O. Leonard, A. F. Clark, M. R. Hernandez, C. J. O'Brien; Gene Transcription Differential Between Optic Nerve Head Astrocytes and Lamina Cribrosa Cells from Normal Human Donors. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5913.
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© ARVO (1962-2015); The Authors (2016-present)
The lamina cribrosa (LC) of the glaucomatous optic nerve head (ONH) demonstrates marked disruption to extracellular matrix (ECM) architecture and composition. ONH astrocytes and LC cells have previously been implicated as modulators of ECM metabolism in the ONH. Our objectives were, therefore, to directly compare the gene expression profile of ONH astrocytes with LC cells cultured from human optic nerve head tissue.
ONH tissue from six human donors with no history of eye disease were used to generate three ONH astrocyte (GFAP-positive) and three LC cell (GFAP-negative) cultures. RNA from LC cells (n=3) was pooled and hybridised to four separate Affymetrix HG-U133A arrays. RNA from astrocytes (n=3) was pooled and hybridised to nine separate Affymetrix HG-U133A arrays. All thirteen arrays were normalised together using robust multichip average (RMA). Differential expression patterns between astrocytes and LC cells were identified using Cluster v3.0 and TreeView v1.04.
Two promiment clusters of differential gene expression were identified between ONH astrocytes and LC cells. Both clusters contained genes involved in ECM metabolism. Cluster A contained genes that were exculsively up regulated in ONH astrocytes versus LC cells, which included: Lysl-oxidase-like 1, palladin, EIF5A, kinesin 2, MAPK kinase 3, PCK-i and dual specificity phosphatase-1. Cluster B contained genes that were exclusively up regulated in LC cells versus astrocytes, which included: adducin 3, IGF-2 receptor, latent TGF-ß binding protein-1, glyoxalase-1, integrin ß-1 and bullous pemphigoid antigen-1.
This is the first study identifying global transcriptional differences between human ONH astrocytes and human LC cells. These data help to further characterise the respective roles of ONH astrocytes and LC cells in ECM remodeling in the ONH in glaucoma.
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