Cao Jiarong, Li Juan, Zheng Haihua, Dong Zhizhang
Department of Ophthalmology, The Second Affiliated Hospital and Yuying Children' S Hospital of Wenzhou Medical University, Wenzhou, 325200, Zhejiang Province, China.
Department of Ophthalmology, Shanxi Ophthalmic Medical Center (Xi'an People Hospital, Xi'an Fourth Hospital), Xi'an, 710004, Shanxi Province, China.
Eur J Med Res. 2025 Jul 16;30(1):635. doi: 10.1186/s40001-025-02898-5.
PURPOSE: This study assesses the impact of high-fat diet on retinal pigment epithelium (RPE) of aged TgAPPswePS1 transgenic mice, focusing on the involvement of RPE cell pyroptosis. METHODS: Twenty-four TgAPPswePS1 transgenic mice (18 months) was randomly divided into Tg group (n = 12) and Fat group (n = 12). Mice in Fat group were fed with high-fat diet consisting of 81.85% standard chow, supplemented with 1% cholesterol, 015% cholic acid, and 17% hydrogenated vegetable oil. Another 12 wild-type C57BL/6J mice were serve as control group. The fundus was examined through Micron IV. The eyes of mice were removed for paraffin-embedding and sectioning. HE staining was carried out to observe the structure of retina and measure retinal thickness. The expressions of amyloid-beta (Aβ), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in RPE, as well as the number of RPE were detected. RESULTS: The RPE in Fat group showed obvious Aβ accumulation (p < 0.0001). Compared with the Tg group, the thickness of retina in the Fat group was significantly reduced (t = 5, p = 0.0075), and the number of RPE was statistically decreased (t = 4.243, p = 0.0132). In addition, the expressions of pyroptosis-related proteins NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 in RPE were significantly increased in Fat group (p < 0.05). CONCLUSIONS: High-fat diet leads to Aβ accumulation in the RPE of aged TgAPPswePS1 transgenic mice, causes RPE damage, in which RPE cell pyroptosis may play a crucial role.
目的：本研究评估高脂饮食对老年TgAPPswePS1转基因小鼠视网膜色素上皮（RPE）的影响，重点关注RPE细胞焦亡的参与情况。 方法：将24只18月龄的TgAPPswePS1转基因小鼠随机分为Tg组（n = 12）和脂肪组（n = 12）。脂肪组小鼠喂食由81.85%标准饲料组成的高脂饮食，补充1%胆固醇、0.15%胆酸和17%氢化植物油。另外12只野生型C57BL/6J小鼠作为对照组。通过Micron IV检查眼底。取出小鼠眼睛进行石蜡包埋和切片。进行HE染色以观察视网膜结构并测量视网膜厚度。检测RPE中淀粉样β蛋白（Aβ）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、半胱天冬酶-1、gasdermin D（GSDMD）、白细胞介素-1β和白细胞介素-18的表达，以及RPE的数量。 结果：脂肪组的RPE显示出明显的Aβ积累（p < 0.0001）。与Tg组相比，脂肪组的视网膜厚度显著降低（t = 5，p = 0.0075），RPE数量在统计学上减少（t = 4.243，p = 0.0132）。此外，脂肪组RPE中焦亡相关蛋白NLRP3、半胱天冬酶-1、GSDMD、白细胞介素-1β和白细胞介素-18的表达显著增加（p < 0.05）。 结论：高脂饮食导致老年TgAPPswePS1转基因小鼠RPE中Aβ积累，引起RPE损伤，其中RPE细胞焦亡可能起关键作用。
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