Acute hyperoxia-induced transcriptional response in the mouse RPE/choroid.
Oxidative stress has been studied in the retinal pigmented epithelium (RPE) in vitro but not in vivo. Our purpose, therefore, was to develop an in vivo model of acute oxidative stress in the C57BL/6J mouse. Mice were exposed to > or = 98% oxygen for 0, 2, or 6 h, and amplified total RNA from the RPE/choroid was applied to microarrays examining about 2200 unique genes. Statistical analysis determined that 642 genes, out of a total of 1349 expressed, were significantly downregulated at only 2 h, only 6 h, or both 2 and 6 h, and a single gene, ubiquitin, was upregulated. These genes are involved in all aspects of cellular functions, and there are no major differences among the three groups. The effect of hyperoxia on the RPE/choroid in vivo appears to be very similar to oxidative stress studies performed with an RPE cell line in vitro. All 11 genes identified as being regulated by all three oxidants in our previous study, and were expressed by mouse, were also differentially regulated by hyperoxia. At least for the initial response to an oxidative challenge, the in vitro ARPE-19 cell line is a reasonable model for in vivo studies.
Weigel
Andrea L
AL
Department of Biological Chemistry, University of California, Davis, Davis, CA 95616, USA. lmhjelmeland@ucdavis.edu
Ida
Hisashi
H
Boylan
Sharon A
SA
Hjelmeland
Leonard M
LM
D000818:Animals; D002829:Choroid / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005136:Eye Proteins / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D018496:Hyperoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D018076:DNA, Complementary; D005136:Eye Proteins; D012333:RNA, Messenger