Transcriptomics

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High-fat and High-sucrose Diets Synergistically Induce reticular pseudo-drusen (RPD)-like Lesions in Rabbits


ABSTRACT: 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 normal diet (ND), high fat diet (HFD), high sucrose diet (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 humor were measured. RNA sequencing was performed to evaluate the retinal transcriptome changes. HFD and HSD had minor effects on lipid profiles but synergistically induced severe dyslipidemia. All diets did not cause obesity. HFSD induced reticular pseudo-drusen (RPD)-like lesions and pigmentary retinal abnormalities. The RPD-like lesions were mainly lipid droplets (retinosomes) in the RPE cells. HFSD induced elevated ocular C3 level and reduced retinal vessel branches, but not retinal inflammation. In conclusion, HFD and HSD can synergistically induce normal-weight dyslipidemia (NWD) and AMD-like retinal lesions. HFSD-fed male Chinchilla rabbits are a good model of early AMD and are valuable to studying NWD and retinosomes.

ORGANISM(S): Oryctolagus cuniculus

PROVIDER: GSE276438 | GEO | 2024/09/05

REPOSITORIES: GEO

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