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M. Steele, D.M. Inman, R.M. Sappington, N. Golestaneh, N. Marsh–Armstrong, D.J. Calkins, P.J. Horner, M.L. Vetter; Whole Retinal Microarray Analysis of DBA/2J Mice: A Model for Glaucoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):48.
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Purpose: Glaucoma is a progressive eye disease that leads to blindness due to loss of retinal ganglion cell (RGC) viability. Little is known about the molecular changes in the retina underlying disease progression. The DBA/2J mouse is an inbred stain that serves as a model for secondary angle–closure glaucoma due to iris atrophy and pigment dispersion, which ultimately leads to increased intraocular pressure. By using microarray analysis we sought to correlate changes in retinal gene expression with disease progression. Methods: Intraocular pressure was monitored in DBA/2J animals by tonopen, and was found on average to increase at around 5 months of age. Thus, we prepared RNA from individual retinas of 3 month old (average IOP=14.2 mmHg) and 8 month old (average IOP = 26.7 mmHg) female animals. We isolated total retinal RNA, then amplified and biotin labeled the RNA for hybridization on high density mouse Affymetrix arrays (U430. The array data was analyzed using two statistical techniques, Ranked Product Analysis (RP) and Significance Analysis of Microarrays (SAM). Results: SAM analysis revealed significant changes in expression of 57 genes in three versus eight month DBA/2J animals, with 27 genes increasing and 30 genes decreasing. Upregulated genes included inflammation–related genes, cell–death/oxidative stress–related genes and genes associated with glial activation. Similar results were obtained with RP analysis. We are currently confirming gene expression changes using quantitative PCR and in situ hybridization on DBA/2J versus C57/B6 control animals, and will also correlate confirmed gene expression changes with disease onset and progression. Conclusions: The DBA/2J retina shows evidence for disease–dependent glial activation and a neuroinflammatory response, as has been observed in several acute glaucoma models. It remains to be determined whether this is a cause or consequence of RGC loss in this glaucoma model.
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