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JL Vittitow, T Borrás; Effects of Four Days of Elevated Intraocular Pressure on Trabecular Meshwork Gene Expression . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1048.
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Purpose: To search for genes induced by increased intraocular pressure (IOP). We have previously shown that elevated IOP significantly increases outflow facility in perfused anterior segments after 4 days. Our goal in this study is to attempt to correlate the changes in outflow facility with changes in gene expression. Methods: High IOP-induced human trabecular meshwork tissues were obtained from perfused anterior segment from post-mortem donors as described.1 cDNA libraries were constructed from eyes exposed to a 35 mmHg increase in IOP for 4 days (n=3) and from contralateral controls maintained at normal pressure (15-18 mmHg). Libraries were labeled and hybridized to a set of identical Human LifeGrid gene arrays (Incyte Genomics) containing 8,400 individual genes and 27 controls. Differential expression was analyzed using ArrayVision software and confirmed by relative quantitative PCR (RQ-PCR). Results: Genes up-regulated after 4 days in each of the three arrays and confirmed by RQ-PCR comprise a different set than those found to be up-regulated after 1 hour and 6 hour insults.1,2 Potentially relevant genes include: genes encoding kinases involved in signal transduction (PIP5K, IP3K, CAMK1 and MAPK14); a regulator of G-protein signaling (RGS11); a sensory neuropeptide (VIP); a regulator of actin elongation and depolymerization (TMOD3); a multi-functional carrier protein (apoD); an inhibitor of calcification (MGP); and a gene localized to a chromosomal region linked to glaucoma (1q21-q25). Conclusions: A number of genes found to be up-regulated after 4 days of elevated IOP are involved in signaling mechanisms including: signal transduction, regulation of G-protein signaling, and neuropeptide synthesis. These results suggest that signal transduction might have an important role in the increase of outflow facility observed in response to four days of elevated pressure. The functional significance of some of these genes is currently under investigation.. 1Gonzalez P, Epstein DL, and Borrás T. Invest Ophthalmol Vis Sci. 2000;41:352-361. 2Vittitow JL, Cherwek DH, Epstein DL, Borrás T, Gonzalez, P. Invest Ophthalmol Vis Sci. 2001; 42:4 #725
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