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Oliver W Gramlich, Dina F Ahram, Markus H Kuehn; Expression of fibrotic and inflammation markers in the human glaucomatous optic nerve head. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4918. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Structural and compositional changes of the optic nerve head (ONH) are a hallmark of glaucoma. This study aims to compare gene expression profiles in ONHs of human donors with primary open angle glaucoma (POAG) and unaffected controls to identify pathways functionally related to tissue remodeling and inflammation.
ONHs were collected from patients with clinically confirmed POAG (n=6) and age-matched control donors (n=6). RNA was extracted from ONHs and assayed using Affymetrix Human Exon 1.0 ST arrays. Differentially expressed genes in glaucoma versus control were identified by ANOVA. Quantitative RT-PCR and immunohistochemistry were performed to validate selected differentially expressed genes.
Microarray analysis revealed 144 genes with reduced and 225 genes with elevated expression in ONHs of POAG donors when compared to controls. Pathway analysis indicates that many of these genes are functionally related to tissue remodeling (43 genes; p=0.015), proliferation (15 genes; p=0.045) and cellular inflammation (5 genes; p=0.028). PTGS2, CMKlR1, NMI, ITGBL1 and FBLN5 are representative markers of these groups and their heightened expression in POAG was verified by RT-PCR (1.2 to 5.4 fold increase). Immunohistochemistry indicated increased expression of FBLN5 as well as signs of cellular infiltrates in the nerve fiber layer and the lamina cribosa of glaucomatous ONHs.
As expected, the glaucomatous changes to the human ONH are associated with altered expression levels of a large number of genes. Interestingly, our data suggest increased expression of both inflammation-related genes and those associated with a fibrotic response. These processes have frequently been observed in concert with one another during CNS injury and are capable of reciprocal stimulation. Fibrosis can engender changes in the biophysical properties of the glaucomatous ONH and will present a barrier to axonal regeneration. The degree to which these events contribute to glaucomatous damage remains to be examined.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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