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T. Favazza, I. Y. Benador, J. A. Mocko, T. C. Vyhovsky, R. M. Hansen, A. B. Fulton, J. D. Akula; Anatomic and Histologic Features in Rat Models of Retinopathy of Prematurity (ROP). Invest. Ophthalmol. Vis. Sci. 2009;50(13):3125.
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ROP is characterized by both neural and vascular abnormalities. Recent electroretinographic data (ERG oscillatory potentials) both from rat models of ROP and human patients with a history of ROP indicate that marked deficits in postreceptor retinal function are features of ROP (Akula et al., 2007). However, ERG parameters differ markedly between rat ROP models. Since the post-receptor retina is supplied by the retinal vasculature, we assessed the retinal vasculature and structure of the neural retina in two rat models of ROP that span the gamut of severity seen in human ROP.
Two rat models of ROP, induced by exposure to alternating 50%/10% oxygen from postnatal day (P) 0 to P14 (50/10 model), or exposure to 75% oxygen from P7 to P14 (75 model), and room-air-reared controls, were studied (N=48). Animals were sacrificed over a range of ages from infancy to adulthood (P15 to >P30). Some rats (n=25) were selected for retinal whole-mounting. Other rats (n=23) were selected for histologic inspection of the retinal laminae. Sections were cut from central and peripheral retina, stained (1% T-blue), and the thicknesses of the retinal laminae measured.
Compared to control retinae which were all completely vascularized, 75 model rats at P20 had avascular zones surrounding the superficial retinal vessels at all retinal eccentricites; these zones comprised ~10% of the retinal surface. In accord with JS Penn et al. (IOVS,1995), 50/10 model rats’ peripheral retinae were avascular at P15-20; the avascular zones comprised ~20% of the retinal surface. By P30, the blood vessels reached the ora in the 50/10 model. Capillary beds of both models at every age appeared more sparsely vascularized than in control rats at any age. Retinal thickness in ROP and control rats did not change significantly with age. Central retina was significantly thicker than the peripheral retina. Inspection of the individual retinal layers revealed that 75 model and control rats’ retinae did not differ significantly, but the post-receptor layers (OPL, INL, IPL, GCL) were all significantly thinner in the 50/10 model. However, there were no significant group×eccentricity interactions.
Both microscopic retinal vascular and histologic inner retinal features differ significantly between control and ROP rat models, and between the models. Interestingly, it is the 50/10 model, characterized by thinning of the inner retinal laminae, that was reported to have attenuated post-receptor ERG oscillatory potentials. Of note, differences in vascular coverage in the central retina vs. the periphery did not equate to differences in histologic inner retinal features.
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