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

IF 4 3区 医学 Q2 CELL BIOLOGY Disease Models & Mechanisms Pub Date : 2024-10-28 DOI:10.1242/dmm.052015
Yujiao Wang, Zhongping Lv, Yongjiang Chen, Xiaobo Cen, Hui Zhang, Danian Chen
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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 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.

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高脂肪和高蔗糖饮食可诱导老年性黄斑变性(AMD)实验兔模型。
老年性黄斑变性(AMD)是导致失明的主要原因。代谢紊乱和饮食是风险因素。我们比较了雄性栗鼠兔长期摄入四种饮食后的血脂状况和视网膜表型。我们用正常饮食 (ND)、高脂饮食 (HFD)、高蔗糖饮食 (HSD) 或高脂高蔗糖饮食 (HFSD) 喂养兔子六个月。使用多模态成像模式和视网膜电图(ERG)检查眼睛。使用 H&E 染色、甲苯胺蓝染色、免疫染色和透射电子显微镜分析视网膜切片。对血清或水液中的脂质和补体C3进行了测定。对视网膜转录组进行了 RNA 测序评估。高密度脂蛋白胆固醇和高密度脂蛋白胆固醇对血脂的影响较小,但协同诱导了严重的血脂异常。所有饮食都不会导致肥胖。HFSD喂养会诱发视网膜病变,如网状假性变性(RPD)和色素异常。RPD样病变主要是RPE细胞周围的脂滴。HFSD 会导致眼部 C3 水平升高,视网膜血管密度降低。总之,HFD 和 HSD 可协同诱导正常体重的血脂异常和 RPD 样视网膜病变。饲喂 HFSD 的雄性金吉拉兔是早期 AMD 的良好模型。
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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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