A High Fat "Western-style" Diet Induces AMD-Like Features in Wildtype Mice

Scope The intake of a "Western-style" diet rich in fats is linked with developing retinopathies including age-related macular degeneration (AMD). Wildtype mice are given a high fat diet (HFD) to determine how unhealthy foods can bring about retinal degeneration. Methods and results Following weaning, female C57BL/6 mice are maintained on standard chow (7% kcal fat, n = 29) or a HFD (45% kcal fat, n = 27) for 12 months. Animals are sacrificed following electroretinography (ERG) and their eyes are analyzed by histology, confocal immunofluorescence, and transmission electron microscopy. HFD mice become obese, but show normal retinal function compared to chow-fed controls. However, diminished beta 3tubulin labeling of retinal cross-sections indicate fewer/damaged neuronal processes in the inner plexiform layer. AMD-linked proteins clusterin and TIMP3 accumulated in the retinal pigment epithelium (RPE) and Bruch's membrane (BrM). Neutral lipids are also deposited in the outer retinae of HFD mice. Ultrastructural analysis reveals disorganized photoreceptor outer segments, collapsed/misaligned RPE microvilli, vacuoles, convoluted basolateral RPE infolds, and BrM changes. Basal laminar-like deposits are also present alongside abnormal choroidal endothelial cells. Conclusions The study shows that prolonged exposure to an unhealthy "Western-style" diet alone can recapitulate early-intermediate AMD-like features in wildtype mice, highlighting the importance of diet and nutrition in the etiology of sight-loss.