Purpose: To examine the susceptibility of photoreceptors to hyperoxic stress in two rat strains, the pigmented Long Evans (LE) and the albino Sprague-Dawley (SD).
Methods: Adult LE and SD rats were exposed to hyperoxia (75% oxygen) for 14 days. Retinas were assessed for electroretinogram (ERG) responses, cell death, and expression of a retinal stress factor.
Results: In the LE strain, exposure to hyperoxia significantly reduced amplitudes of rod a-wave, rod b-wave and cone b-wave components of the ERG, and caused a 55-fold increase in photoreceptor cell death rates, and an upregulation of GFAP expression. In the SD strain, hyperoxic exposure had no measurable effect on the ERG response of rods or cones, and resulted in a modest (5-fold) increase in the rate of photoreceptor cell death.
Conclusions: In LE and SD strains, hyperoxia induces cell death specific to photoreceptors. The effect is an order of magnitude more severe in the pigmented LE strain suggesting a strong genetic component to oxygen sensitivity, as reported previously between the albino Balb/C and pigmented C57BL/6 strains of mice.
This is a preview of subscription content, log in to check access
Burke JM, Henry MM, Zareba M et al (2007) Photobleaching of melanosomes from retinal pigment epithelium: I. Effects on protein oxidation. Photochem Photobiol 83:920–924CrossRefPubMedGoogle Scholar
Chan-Ling T, Stone J (1993) Retinopathy of prematurity: origins in the architecture of the retina. Prog Retin Eye Res 12:155–178Google Scholar
Chrysostomou V, Stone J, Stowe S et al (2008) The status of cones in the rhodopsin mutant P23H-3 retina: light-regulated damage and repair in parallel with rods. Invest Ophthalmol Vis Sci 49:1116–1125CrossRefPubMedGoogle Scholar
Dunford R, Land EJ, Rozanowska M et al (1995) Interaction of melanin with carbon- and oxygen-centered radicals from methanol and ethanol. Free Radic Biol Med 19:735–740CrossRefPubMedGoogle Scholar
Gao G, Li Y, Fant J et al (2002) Difference in ischemic regulation of vascular endothelial growth factor and pigment epithelium-derived factor in brown norway and Sprague-Dawley rats contributing to different susceptibilities to retinal neovascularization. Diabetes 51:1218–1225CrossRefPubMedGoogle Scholar
Geller S, Krowka R, Valter K et al (2006) Toxicity of hyperoxia to the retina: evidence from the mouse. Adv Exp Med Biol 572:425–437CrossRefPubMedGoogle Scholar
Nixon PJ, Bui BV, Armitage JA et al (2001) The contribution of cone responses to rat electroretinograms. Clin Exp Ophthalmol 29:193–196CrossRefGoogle Scholar
Noell WK (1955) Visual cell effects of high oxygen pressures. Fed Proc 14:107–108Google Scholar
Okoye G, Zimmer J, Sung J et al (2003) Increased expression of brain-derived neurotrophic factor preserves retinal function and slows cell death from rhodopsin mutation or oxidative damage. J Neurosci 23:4164–4172PubMedGoogle Scholar
Padnick-Silver L, Kang Derwent JJ, Giuliano E et al (2006) Retinal oxygenation and oxygen metabolism in Abyssinian cats with a hereditary retinal degeneration. Invest Ophthalmol Vis Sci 47:3683–3689CrossRefPubMedGoogle Scholar
Rozanowska M, Sarna T, Land EJ et al (1999) Free radical scavenging properties of melanin interaction of eu- and pheo-melanin models with reducing and oxidising radicals. Free Radic Biol Med 26:518–525CrossRefPubMedGoogle Scholar
Smit-McBride Z, Oltjen SL, Lavail MM et al (2007) A strong genetic determinant of hyperoxia-related retinal degeneration on mouse chromosome 6. Invest Ophthalmol Vis Sci 48:405–411CrossRefPubMedGoogle Scholar
Stone J, Maslim J, Valter-Kocsi K et al (1999) Mechanisms of photoreceptor death and survival in mammalian retina. Prog Retin Eye Res 18:689–735CrossRefPubMedGoogle Scholar
van Wijngaarden P, Brereton HM, Coster DJ et al (2007) Genetic influences on susceptibility to oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 48:1761–1766CrossRefPubMedGoogle Scholar
van Wijngaarden P, Coster DJ, Brereton HM et al (2005) Strain-dependent differences in oxygen-induced retinopathy in the inbred rat. Invest Ophthalmol Vis Sci 46:1445–1452CrossRefPubMedGoogle Scholar
Walsh N, Bravo-Nuevo A, Geller S et al (2004) Resistance of photoreceptors in the C57BL/6-c2J, C57BL/6 J, and BALB/cJ mouse strains to oxygen stress: evidence of an oxygen phenotype. Curr Eye Res 29:441–447CrossRefPubMedGoogle Scholar
Wellard J, Lee D, Valter K et al (2005) Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia. Visual Neurosci 22:222–229Google Scholar
Yamada H, Yamada E, Hackett SF et al (1999) Hyperoxia causes decreased expression of vascular endothelial growth factor and endothelial cell apoptosis in adult retina. J Cell Physiol 179:149–156CrossRefPubMedGoogle Scholar
Ye T, Simon JD, Sarna T (2003) Ultrafast energy transfer from bound tetra(4-N,N,N,N-trimethylanilinium) porphyrin to synthetic dopa and cysteinyldopa melanins. Photochem Photobiol 77:1–4CrossRefPubMedGoogle Scholar
Yu D-Y, Cringle SJ, Su E-N et al (2000) Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat. Invest Ophthalmol Vis Sci 41:3999–4006PubMedGoogle Scholar
Yu D-Y, Cringle S, Valter K et al (2004) Photoreceptor death, trophic factor expression, retinal oxygen status, and photoreceptor function in the P23H rat. Invest Ophthalmol Vis Sci 45:2013–2019CrossRefPubMedGoogle Scholar
Zadlo A, Rozanowska MB, Burke JM et al (2007) Photobleaching of retinal pigment epithelium melanosomes reduces their ability to inhibit iron-induced peroxidation of lipids. Pigment Cell Res 20:52–60CrossRefPubMedGoogle Scholar
Zareba M, Sarna T, Szewczyk G et al (2007) Photobleaching of melanosomes from retinal pigment epithelium: II. Effects on the response of living cells to photic stress. Photochem Photobiol 83:925–930CrossRefPubMedGoogle Scholar
Zhang X, Erb C, Flammer J et al (2000) Absolute rate constants for the quenching of reactive excited states by melanin and related 5,6-dihydroxyindole metabolites: implications for their antioxidant activity. Photochem Photobiol 71:524–533CrossRefPubMedGoogle Scholar