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

Due to a possible link in humans between atherosclerosis, a high-fat diet, and the development of age-related retinal degenerations, we investigated retinal changes with age and diet in high-fat-fed C57BL/6 mice, a mouse model of human atherosclerosis.

We fed C57BL/6J mice either a normal chow diet or an atherogenic diet containing 15% total fat for either 15, 30 or 45 weeks. We sacrificed the animals and examined the eyes using fluorescence microscopy, light microscopy and transmission electron microscopy.

At 15 weeks, in high-fat-fed mice, there was an increase in the number of autofluorescent granules in the retinal pigment epithelium (RPE) compared to chow-fed mice. By light microscopy, we noted no remarkable differences in the inner retinal layers between mice fed either diet for 15 or 30 weeks. In contrast, we noted major changes in transmission electron micrographs from the 30 week high-fat group. In the RPE, these included: (1) an increase in the number and size of autophagocitic and empty cytoplasmic vacuoles; (2) accumulations of lipid-like droplets in the cytoplasm, and (3) RPE atrophy. Changes in Bruch's membrane included: (1) thickening; (2) fragmentation of the elastic lamina, and (3) the accumulation of electron dense particulate and vesicular structures within the inner and outer collagenous zones. These changes were not seen in mice fed normal diets even at 45 weeks.

We suggest that this model may prove useful for investigations into mechanisms on the effects of diet on the RPE and Bruch's membrane.