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M. Rudolf, U. Schloetzer–Schrehardt, Z. Aherrazou, P. Kaczmarek, U. Schmidt–Erfurth; Ultrastructural degenerative changes in Bruch's membrane, Retinal Pigment Epithelium (RPE) and Photoreceptors of LDL–receptor–knock–out mice . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2287.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the pathogenesis of age–related macular degeneration (AMD) with respect to serum lipids in an established arteriosclerosis mouse model with low–density lipoprotein (LDL) receptor deficiency. Methods: 8–months–old LDL–receptor–deficient mice (C57BL/6 LDL–r(–)) and C57BL/6 controls were fed a standard rodent diet or a high fat diet western type for two months. Animals were sacrificed and serum cholesterol levels were determined. Eyes were examined by light microscopy (LM) and transmission electron microscopy (TEM). Oil Red O staining was performed. Results: Control animals did not exhibit any visible changes by LM /TEM after standard diet (average Bruch's membrane (BM) thickness 0,5µm, RPE height 8µm). Serum cholesterol levels were elevated in controls after high fat diet, but were significantly higher in LDL–receptor–deficient mice after standard diet. Serum cholesterol was highest in LDL–receptor–deficient mice after high fat diet. Corresponding to serum cholesterol levels, the thickness of BM increased up to 0,8µm with condensation of collagenous und elastic fibers and loss of regular BM structure. With elevated serum cholesterol, lipid inclusions (Oil Red O +) were found in BM focally, however, BM lipids were consistently found only in knock–out animals following high fat diet. Changes within the RPE were only documented in LDL–receptor–deficient mice associated with lipid vacuoles and lipofuscein–like deposits. The RPE was flattened to 5µm, cell organelles (ribosomes, mitochondria, endoplasmatic reticulum) were increased and the basal labyrinth and microvilli were reduced. Photoreceptor outer segments showed focal degeneration with vacuoles, especially in LDL–receptor–deficient mice after high fat diet. Conclusions: LDL–receptor–deficient mice exhibit distinct degenerative changes in BM, RPE and outer photoreceptor segments. Histologic changes appeared to correlate with serum cholesterol. The changes are similar to those seen in early AMD and may help to investigate the pathogenesis of AMD.
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