High-fat and high-sucrose diets induce an experimental rabbit model for age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is a leading cause of blindness. Metabolic disorders and diets are risk factors. We compared lipid profiles and retinal phenotypes with long-term feeding of four diets in male Chinchilla rabbits. Animals were fed with a normal diet (ND), high-fat (HFD), high-sucrose (HSD), or high-fat and high-sucrose diet (HFSD) for six months. The eyes were examined using multimodal imaging modalities and electroretinogram (ERG). Retinal sections were analyzed using H&E staining, toluidine blue staining, immunostaining, and transmission electron microscopy. Lipids and complement C3 in serum or aqueous humour were measured. RNA sequencing was performed to evaluate the retinal transcriptomes. HFD and HSD had minor effects on lipid profiles but synergistically induced severe dyslipidemia. All diets did not cause obesity. HFSD feeding induced retinal lesions like reticular pseudo-drusen (RPD) and pigmentary abnormalities. The RPD-like lesions were mainly lipid droplets around RPE cells. HFSD induced elevated ocular C3 levels and reduced retinal vessel density. In conclusion, HFD and HSD can synergistically induce normal-weight dyslipidemia and RPD-like retinal lesions. HFSD-fed male Chinchilla rabbits are a good model of early AMD.