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Z. Yang, M.E. Pease, K. Stormes, J. Kielczewski, H.A. Quigley, D.J. Zack; Gene Expression Alterations in Rat Retina After Experimental Elevation of Intraocular Pressure . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1563.
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© ARVO (1962-2015); The Authors (2016-present)
We studied gene expression changes in rats with experimentally–induced intraocular pressure (IOP) elevation and with optic nerve transection to elucidate molecular mechanisms of retinal ganglion cell (RGC) death.
Laser treatment of trabecular meshwork was used to induce unilateral IOP elevation in albino Wistar rats (N = 36). In parallel, full transection of rat optic nerve was performed (N = 36). Retinas were harvested 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 8 weeks after laser treatment, and total RNA was isolated with Trizol reagent from experimental and fellow eyes. The expression levels of candidate genes in RNA samples were examined by real time RT–PCR (QPCR). Candidate genes included pathways involved in RGC function, cell signaling, and apoptosis, and genes found changed in our microarray studies of human glaucoma samples (Farkas., et al, unpublished data). In addition, pools of RNA from each time point are being analyzed with Affymetrix rat genome 230 2.0 arrays. Arrays are also being performed on retinas at various time points after optic nerve transection. These array results will be confirmed by QPCR and in situ hybridization studies.
Experimental IOP elevation of IOP caused expression level alterations in genes encoding transcription factors, signal molecules, extracellular matrix proteins, intracellular signal transducers, neurotransmitter transporters, and apoptosis–related proteins. Expression levels of Solute carrier family 17 A6 (SLC17A6), POU–domain transcription factor Pou4F2, and Thy–1, are rapidly down–regulated after experimental IOP elevation and optic nerve transection, whereas expressions of endothelin–2, Endothelin receptor B (EdnrB), and Serum/glucocorticoid regulated kinase 2 are up–regulated. Changes after IOP elevation and after optic nerve transection showed strong similarity.
Profiling gene expression change in rat retina following experimental IOP elevation and axotomy reveals a number of overlapping genes with similar altered expression patterns, despite distinct changes that are specific to each condition. Ongoing investigation on these findings will hopefully provide insight into the pathogenesis of RGC loss in glaucoma.
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