oxygen diffuses to photoreceptors from choroidal vessels located behind the retinal pigment epithelium (RPE). Presumably because the choroidal vessels lie external to the photoreceptors that they serve, the flow of blood through the choroid is not regulated in response to levels of oxygen or other local metabolic factors (Chan-Ling and Stone 1993; Stone et al. 1999). As a consequence, photoreceptors, unlike most other tissues in the body, are poorly protected against fluctuations of oxygen.

Although all photoreceptors have a pre-determined vulnerability to hyperoxia due to the retinal architecture, the degree of this vulnerability appears to differ between strains of mouse. Photoreceptors in the adult pigmented C57BL/6 J mouse strain are relatively vulnerable to hyperoxia, while those in the albino BALB/cJ, C57BL/6–c2 J and A/J strains are relatively resistant (Yamada et al. 1999; Walsh et al. 2004; Smit-McBride et al. 2007). These strain-dependent differences suggest a genetic basis for photoreceptor sensitivity to oxygen stress and, recently, a strong determinant for the A/J–C57BL/6 difference has been localized to chromosome 6 (Smit-McBride et al. 2007).

To date, the vulnerabilities of different adult rat strains to oxygen stress have not been explored. However, work in the neonatal rat suggests that, like the mouse, there are strain-dependent differences to oxygen stress. Pigmented Dark Agouti, Hooded Wistar and Brown Norway rats are more vulnerable to oxygen-induced retinopathy than albino Sprague-Dawley, Fischer 344, Wistar-Furth and Lewis rats (Gao et al. 2002; van Wijngaarden et al. 2005). Using formal backcross analysis, the genetic basis of the Dark Agouti-Fischer 344 difference has been modeled using an autosomal dominant pattern of inheritance (van Wijngaarden et al. 2007).

Here, we test the impact of hyperoxia on photoreceptors in the mature retina of two rat strains; the pigmented Long Evans (LE) and the albino SpragueDawley (SD).

54.2 Methods

54.2.1 Animal Strains and Oxygen Exposure

All procedures were in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Pigmented Long Evans (LE) and albino Sprague-Dawley (SD) rats aged 90–150 days were used. All animals were born, raised and exposed to hyperoxia in dim cyclic illumination (12 h 5 lux/12 h dark). Animals were exposed to hyperoxia (75% oxygen) for 14 days by placing litter boxes inside a plexiglass chamber in which the oxygen concentration was controlled by a feedback system (OxyCycler, Biospherix).

54.2.2 Electroretinography

Animals were dark-adapted overnight and prepared for recording in dim red illumination as described previously (Chrysostomou et al. 2008). Following previous reports, (Nixon et al. 2001), responses to a standard test flash (44.5 cds/m2) were