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Peter van Wijngaarden, Helen M. Brereton, Douglas J. Coster, Keryn A. Williams; Genetic Influences on Susceptibility to Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(4):1761-1766. doi: 10.1167/iovs.06-0531.
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purpose. To investigate the inheritance of susceptibility to oxygen-induced retinopathy in the rat with the use of formal backcross analysis.
methods. Neonatal offspring of inbred albino Fischer 344 (F344) and pigmented Dark Agouti (DA) crosses and F1×F344 and F1×DA backcrosses were exposed to alternating 24-hour cycles of hyperoxia (80% oxygen in air) and normoxia (21% oxygen in air) for 14 days. Retinal avascular area was analyzed by staining with Griffonia simplicifolia isolectin B4, a marker of vascular endothelial cells. Expression of erythropoietin (EPO) mRNA in retinas was quantified by real-time reverse-transcription polymerase chain reaction.
results. Oxygen-exposed offspring of two F344×DA F1 crosses showed retinal avascular areas and ocular and coat pigmentation that were similar to those of the DA strain. Mean retinal avascular area was 73%. Offspring of two DA×F1 backcrosses were similar to F344×DA F1 pups, with pigmented eyes and coats and a mean retinal avascular area of 76%. In contrast, offspring of two F344×F1 backcrosses exhibited a range of eye and coat pigmentation. Mean retinal avascular area of pigmented offspring of the F344×F1 backcrosses was 71% (P < 0.001 compared with F344 rats). Mean avascular area of albino offspring of the F344×F1 backcrosses was 27% (P > 0.05 compared with F344 rats). The normalized expression of EPO mRNA was 3.01 ± 1.00 in retinas from pigmented F344×F1 backcross offspring compared with 1.31 ± 0.69 for albino offspring (P < 0.001).
conclusions. Segregation of the susceptibility trait to oxygen-induced retinopathy in the DA and F344 rat strains is associated with pigmentation and erythropoietin expression and can be modeled using an autosomal dominant pattern of inheritance.
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