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A. C. Ziesel, M. A. Chrenek, R. M. Darrow, L. Barsalou, D. T. Organisciak, P. W. Wong; Gene Expression Changes Observed During Acute Light-Induced Retinal Damage. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4482.
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Acute light-induced retinal damage (LIRD) in rodents is an accepted model of chronic oxidative stress leading to retinal degeneration. While the process is not entirely understood, it is believed that the time of peak induction of heme oxygenase-1 expression represents peak oxidative stress in the retina. To examine in greater detail other gene expression changes at this point we performed a differential microarray analysis.
We subjected dark-reared animals to sixteen hours acute green light treatment (1,200 lux), starting at 9AM, after which the animals were euthanized and retinae dissected. Included in the experimental design were untreated animals sacrificed at experiment time zero and at the end point of the experiment. For each of the three conditions considered, retinal RNA was obtained from three male Sprague-Dawley rats, a probe was made and hybridized against Illumina’s RatRef-12 expression BeadChips. Raw data was generated using Illumina’s BeadStudio software, which was then analyzed using the lumi, limma, annotate and GOstats R packages from BioConductor.
Statistically significant changes in expression of genes involving apoptotic commitment (such as Lcn2, Ccl2), remodeling of ECM and lipid bilayers (such as Mmp3, Timp1, Adfp) and the inflammatory response (such as Cxcl10, C1s, Serpina3n) were observed. Functional annotation pattern changes were observed, including statistically significant changes pertaining to chaperone activity, translational regulation, redox potential and macromolecule metabolic processes.
Detailed characterization of the state of stressed cells approaching or in the process of apoptosis provides insight into potential therapies, as well as eliminating unrealistic alternatives. These data allow a more precise understanding of the relationships within the dynamic genetic network changes that occur during LIRD and by extension, human degenerative retinal conditions.
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