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D.A. DiLoreto, D.J. Calkins; An ultrastructural study of the pathology of the retinal pigment epithelium, Bruch’s membrane, and choriocapillaris in the aging Fischer 344 rat: a model of age–related macular degeneration . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1778.
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Purpose: To describe the ultrastructural changes that occur in the retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in the aging eye of the Fischer 344 (F344) rat and compare them with those associated with age–related macular degeneration (AMD) in humans. Methods: Fischer 344 rat retinas were embedded for ultrastructural study from 24 month old animals (n=4 animals, 8 eyes). Twenty–four month old F344/Brown Norway hybrids (n= 4 animals, 8 eyes) were used as controls. Results: Twenty–four month old F344 rats showed progressive changes in the RPE/Bruch's/choriocapillaris complex increasing anteriorly as the the ora serrata was approached. Early peripheral changes of the RPE included an increased number of basal infoldings, an increased number of phagolysosomes, both hypertrophy and atrophy, and inclusion of fenestrated vasculature. Bruch’s membrane showed spots of considerable thinning, but most prominent was the severe thickening. In some areas it was vascularized and infiltrated with fibroblasts. Choriocapillaris was transformed to fibrovascular tissue in the most severely affected regions. Twenty–four month old F344/BN hybrids showed only mild RPE changes and no significant changes in Bruch's membrane or the choriocapillaris. Conclusions: Age–related ultrastructural changes in the F344 rat retina have correlates to AMD in human eyes. Because of the slow nature of these changes to develop, their easy accessibility to purchase through the NIA, and being one the of the three chosen rat strains for aging studies, this model provides a way to study the earliest changes and mechanisms of RPE, Bruch’s membrane, and choriocapillaris pathology that may have overlap with human disease.
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