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Purpose <p>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.</p> Methods <p>Twenty-four TgAPPswePS1 transgenic mice (18 months) was randomly divided into Tg group (<i>n</i> = 12) and Fat group (<i>n</i> = 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.</p> Results <p>The RPE in Fat group showed obvious Aβ accumulation (<i>p</i> &lt; 0.0001). Compared with the Tg group, the thickness of retina in the Fat group was significantly reduced (t = 5, <i>p</i> = 0.0075), and the number of RPE was statistically decreased (t = 4.243, <i>p</i> = 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 (<i>p</i> &lt; 0.05).</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月16日

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  • Jiarong Cao,
  • Juan Li,
  • Haihua Zheng,
  • Zhizhang Dong

摘要

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.