Pathologic changes in the retinal pigment epithelium and Bruch's membrane of fat-fed atherogenic mice

Purpose. Due to a possible link in humans between atherosclerosis, a high-f at diet, and the development of age-related retinal degenerations, we inves tigated retinal changes with age and diet in high-fat-fed C57BL/6 mice, a m ouse model of human atherosclerosis. Methods. We fed C57BL/6J mice either a normal chow diet or an atherogenic d iet containing 15% total fat for either 15, 30 or 45 weeks. We sacrificed t he animals and examined the eyes using fluorescence microscopy, light micro scopy and transmission electron microscopy. Results. At 15 weeks, in high-fat-fed mice, there was an increase in the nu mber of autofluorescent granules in the retinal pigment epithelium (RPE) co mpared to chow-fed mice. By light microscopy, we noted no remarkable differ ences in the inner retinal layers between mice fed either diet for 15 or 30 weeks. In contrast, we noted major changes in transmission electron microg raphs from the 30 week high-fat group. In the RPE, these included: (1) an i ncrease in the number and size of autophagocitic and empty cytoplasmic vacu oles: (2) accumulations of lipid-like droplets in the cytoplasm, and (3) RP E atrophy. Changes in Bruch's membrane included: (1) thickening; (2) fragme ntation of the elastic Lamina? and (3) the accumulation of electron dense p articulate and vesicular structures within the inner and outer collagenous zones. These changes were not seen in mice fed normal diets even at 45 week s. Conclusions. We suggest that this model may prove useful for investigations into mechanisms on the effects of diet on the RPE and Bruch's membrane.