Abstract
Abstract: :
Purpose: To determine whether antioxidant treatment of rats alters retinal gene expression prior to or after intense light induced degeneration. Methods: Adult male Sprague Dawley rats were pretreated with the antioxidant dimethylthiourea (DMTU) 2X IP, 500mg/kg, or saline and then exposed to intense light for 8 hrs starting at 1am. Light exposure at 1am causes extensive visual cell damage, which is completely prevented by DMTU. Retinas were excised from groups of 3 rats from each of 3 separate experiments and RNA extracted for use in DNA microarray analysis. Gene expression profiles were determined using Affymetrix rat genome U34A Genechips, containing approximately 7000 known genes. Genes identified as having significant alterations in mRNA levels met a 2-fold change threshold, presented with statistically relevant changes in a Mann-Whitney Test (P55% of comparative analyses). Results: In unexposed control rats DMTU treatment led to increases in 20 genes and decreases in 6 genes, relative to the saline vehicle. Light exposure of DMTU or saline treated rats resulted in increased expression of approximately 100 genes and to decreases in 25 and 58 genes, respectively. Comparing DMTU with saline in light exposed rats the expression of 67 genes increased and 125 genes decreased. Among the variety of transcription factors whose expression was altered, significant increases in c-fos and some jun family members occured in saline treated light exposed rat retinas. However, DMTU treatment caused a significant reduction in the expression of c-fos and JunB. Conclusion: In unexposed control rats DMTU treatment led to increases in 20 genes and decreases in 6 genes, relative to the saline vehicle. Light exposure of DMTU or saline treated rats resulted in increased expression of approximately 100 genes and to decreases in 25 and 58 genes, respectively. Comparing DMTU with saline in light exposed rats the expression of 67 genes increased and 125 genes decreased. Among the transcription factors whose expression was altered, significant increases in c-fos and some jun family members were found in saline treated light exposed rat retinas. DMTU treatment caused a significant reduction in the expression of c-fos and JunB.
Keywords: 537 radiation damage: light/UV • 517 photoreceptors • 316 animal model