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Updated: Jun 14, 2025
Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
Fine particulate matter potentiates Th17-cell pathogenicity in experimental autoimmune uveitis via ferroptosis
Yaning Liu1, Wanyun Zhang1, Hongmiao Wang1
1The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
The effect of fine particulate matter (PM2.5) on the development of uveitis remains unclear. Therefore, this study was designed to investigate the role of PM2.5 in experimental autoimmune uveitis (EAU) and its potential mechanism. Our results showed that PM2.5 could exacerbate the activity of EAU, as evidenced by severer clinical and pathological changes, correlated with elevated Th17 cells frequency and IL-17A expression. Proteomic analysis revealed ferroptosis was the most significant pathway. In vivo, the levels of Fe2+, ROS, lipid ROS, and malondialdehyde, as well as the expression of TFRC, HMOX1, FTH1, and FTL1 in CD4+ T cells were increased, while GSH/GSSG ratio and the expression of ACSL1 and GPX4 were decreased after PM2.5 exposure. In vitro, the expression of TFRC and HMOX1 were increased, while the expression FTH1, FTL1, ACSL1, and GPX4 were decreased after PM2.5 exposure. Ferrostatin-1 effectively alleviated PM2.5-induced intraocular inflammation and suppressed the frequency of Th17 cells. These results suggest that PM2.5 could aggravate intraocular inflammation and immune response in EAU mice through ferroptosis. Ferroptosis could be a potential marker for the prevention and treatment of uveitis.
Insights
Fine particulate matter (PM2.5) exposure worsens experimental autoimmune uveitis (EAU) by promoting ferroptosis, a cell death pathway. This highlights ferroptosis as a potential therapeutic target for PM2.5-induced uveitis.
Area of Science:
- Immunology
- Environmental Health
- Ophthalmology
Background:
- The impact of fine particulate matter (PM2.5) on uveitis development is not well understood.
- Uveitis is an inflammatory eye disease with significant visual impairment potential.
Purpose of the Study:
- To investigate the role of PM2.5 in experimental autoimmune uveitis (EAU).
- To elucidate the underlying mechanisms of PM2.5-induced uveitis exacerbation.
Main Methods:
- Utilized a mouse model of EAU exposed to PM2.5.
- Conducted proteomic analysis, in vivo and in vitro cellular assays, and measured inflammatory markers.
- Assessed the therapeutic effect of ferrostatin-1, an inhibitor of ferroptosis.
Main Results:
- PM2.5 exposure exacerbated EAU, increasing clinical and pathological severity.
- Elevated Th17 cell frequency and IL-17A expression were observed.
- Proteomic analysis identified ferroptosis as a key pathway, with altered iron metabolism, oxidative stress markers, and ferroptosis-related gene expression in CD4+ T cells.
- Ferrostatin-1 treatment ameliorated PM2.5-induced inflammation and reduced Th17 cell frequency.
Conclusions:
- PM2.5 aggravates intraocular inflammation and immune responses in EAU by inducing ferroptosis.
- Ferroptosis is implicated as a critical mechanism in PM2.5-mediated uveitis.
- Targeting ferroptosis may offer a novel strategy for preventing and treating PM2.5-related uveitis.
