High-fat diet activates pyroptosis of retinal pigment epithelial cells in aged TgAPPswePS1 transgenic mice

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.

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.

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).

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.