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Meg Ramos, Iona Raymond, Corine Ghosn, James Burke, Scott Whitcup; Progressive RPE Dystrophy in Dutch Belt Rabbits. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6436.
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Retinal pigment epithelium (RPE) dystrophies like Stargardt’s disease are characterized by progressive RPE accumulation of intracellular autofluorescent (AF) lipopigments of which lipofuscin is a major component. RPE dysfunction is associated with incomplete degradation of photoreceptor outer segments (POS) due to altered membrane proteins resulting from genetic mutations and/or vitamin E deficiencies. RPE necrosis, POS degeneration and retinal atrophy occur end-stage. In this study, we describe the clinical and histopathologic features of Dutch Belt (DB) rabbits identified with early onset, progressive RPE dystrophy associated with the accumulation of AF, PAS + cytoplasmic granules, POS degeneration and retinal atrophy.
In-vivo imaging (OCT, color/AF fundus photography) was used to grade and monitor lesions from 24 eyes with varying degrees of disease severity. Histopathology and electron microscopy (EM) were performed on eyes using standard techniques and fluorescent immunohistochemistry (IHC) was used for RPE65 and CRALBP. Serum vitamin E concentrations were determined by high-performance-liquid-chromatography (HPLC).
RPE degeneration presented as a continuum of lesions primarily localized to the visual streak. Early changes consisted of hypertrophy of individual RPE cells with cytoplasmic inclusions. Small focal lesions first detectable by imaging were coincident with the involvement of a few adjacent RPE with hypertrophy, inclusions, and pigment abnormalities. Affected cells were AF, PAS+, and immunoreactive to RPE65 and CRALBP. Marked distention of RPE by pigmented cytoplasmic granules was associated with POS degeneration in larger lesions. Progression was characterized by increased AF, reduced reactivity to RPE65 and CRALBP, migrant RPE, deposits of cell debris, retinal detachment and atrophy.By EM, membranous whorls reminiscent of POS were present in cytoplasmic inclusions (~100 um). RPE were distended by apical granules characteristic of lipofuscin and melanolipofuscin. Progressive degeneration included loss of tight junctions, distortion of apical villi, detachment, and loss of polarity.Serum vitamin E concentrations were within normal limits (1-3 ppm).
Progressive RPE dystrophy of DB rabbits may be useful for modeling the pathogenesis of human retinal disease and help in understanding disease pathogenesis and identifying therapeutic targets.
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