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SF Geller, J Stone; Evidence That Oxygen Stress Alters mRNA Expression in the Rodent Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4524.
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Purpose: Oxygen is proving to be an important molecule in the progression of a multitude of diseases such as cancer, stroke and diabetes. In the retina, oxygen is likely to play a unique role in both inner and outer retinal physiology due to the close apposition and dependence of photoreceptors on the choroidal blood supply. Indeed, relatively small changes in choroidal oxygen tension directly influence outer retinal PO2. Furthermore, oxygen may contribute to the progression of a number of retinal diseases including macular degeneration, diabetic retinopathy, retinopathy of prematurity, and retinitis pigmentosa. The goal of the current study was to identify altered mRNA expression of oxygen-related molecules, photoreceptor-specific proteins, growth factors, and other retina-associated factors following oxygen stress. Methods: Mice and rats were subjected to several different oxygen regimes: direct hypoxic (10%) or hyperoxic (70%) oxygen environments; oxygen challenge followed by a return to room air; extended hyperoxia (75%), and finally; an animal model of retinopathy of prematurity where mice are subjected to 75% oxygen for 5 days followed by room air. Retinas were collected and total RNA was isolated, purified, quantified, and reverse transcribed. Semi-quantitative PCR was used to assess relative mRNA levels of growth factors, neurotrophic factors, transcription factors, ligand receptors, amino acid transporters, and stress response genes in both the rat and mouse. Control animals were subjected to room air (21% O2). Results: The results of this screen suggest that both subtle (particularly in the mouse) and dramatic (particularly in the rat) changes in mRNA expression occur in response to hypoxia, hyperoxia, or both. PCR analysis suggests that specific members within any given class of molecules (e.g. growth factors) may be similarly up- or down-regulated, while other family members are reciprocally regulated by high or low oxygen levels. Conclusion: These data suggest that both hypoxia and hyperoxia have immediate and distinct consequences on gene expression. A screen of well-studied retinal genes suggests that altering the concentration of inspired oxygen has distinct and identifiable effects on mRNA expression. This abnormal expression may contribute to altered physiology of retinal cells, particularly photoreceptors, whenever oxygen concentration in the inspired air is modified. Although oxygen-induced mRNA expression may be harmless and/or part of a self-protective mechanism, the consequences of extended expression of such "reactive" factors may be serious, and may play a role in the progression of photoreceptor degenerations.
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