Natoli, RiccardoProvis, JanValter (Valter-Kocsi), KrisztinaStone, Jonathan2015-12-101090-0535http://hdl.handle.net/1885/60816Purpose: Hyperoxia is specifically toxic to photoreceptors, and this toxicity may be important in the progress of retinal dystrophies. This study examines gene expression induced in-the C57BL/6J mouse retina by hyperoxia over the 14-day period during which photoreceptors first resist, then succumb to hyperoxia. Methods: Young adult C57BL/6J mice were exposed to hyperoxia (75% oxygen) for up to 14 days. On day 0 (control), day 3, day 7, and day 14, retinal RNA was extracted and processed on Affymetrix GeneChip® Mouse Genome 430 2.0 arrays. Microarray data were analyzed using GCOS Version 1.4 and GeneSpring Version 7.3.1. For 15 genes, microarray data were confirmed using relative quantitative real-time reverse transcription polymerase chain reaction techniques. Results: The overall numbers of hyperoxia-regulated genes increased monotonically with exposure. Within that increase, however, a distinctive temporal pattern was apparent. At 3 days exposure, there was prominent upregulation of genes associated with neuroprotection. By day 14, these early-responsive genes were downregulated, and genes related to cell death were strongly expressed. At day 7, the regulation of these genes was mixed, indicating a possible "transition period" from stability at day 3 to degeneration at day 14. When functional groupings of genes were analyzed separately, there was significant regulation in genes responsive to stress, genes-known to cause human photoreceptor dystrophies and genes associated with apoptosis. Conclusions: Microarray analysis of the response of the retina to prolonged hyperoxia demonstrated a temporal pattern involving early neuroprotection and later cell death, and provided insight into the mechanisms involved in the two phases of response. As hyperoxia is a consistent feature of the late stages of photoreceptor degenerations, understanding the mechanisms of oxygen toxicity may be important therapeutically.Keywords: dystrophin; oxygen; RNA; animal experiment; animal model; animal tissue; apoptosis; article; C57BL 6 mouse; cell death; down regulation; female; gene expression regulation; gene function; genetic analysis; genetic association; genetic stability; human; hy20082016-02-24