2. Academic Validation
  3. Single-cell RNA sequencing reveals beneficial mechanisms of Exendin-4 in autoimmune uveitis

Single-cell RNA sequencing reveals beneficial mechanisms of Exendin-4 in autoimmune uveitis

  • Biochem Pharmacol. 2025 Oct 30;243(Pt 1):117483. doi: 10.1016/j.bcp.2025.117483.
Dongting Wu 1,  Yuehan Gao 1,  Yingying Wen 2,  Yihan Zhang 3,  Yuxi Chen 4,  Lei Zhu 3,  Xuening Peng 5,  Zeyu Pan 1,  Danping Huang 1,  Shuyan Qin 6,  He Li 7,  Wenru Su 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, China.
  • 2 Bengbu Medical University, Bengbu 233000, China.
  • 3 State Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200001, China.
  • 4 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, China; Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai Key Laboratory of Visual Impairment and Restoration, NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200030, China.
  • 5 Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
  • 6 The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian 223800, China. Electronic address: sqyyyk1@163.com.
  • 7 State Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200001, China. Electronic address: 847540515@qq.com.
  • 8 State Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200001, China. Electronic address: suwenru@sjtu.edu.cn.
PMID: 41173056 DOI: 10.1016/j.bcp.2025.117483
Abstract

Autoimmune uveitis (AU), a sight-threatening inflammatory eye disease, is a leading cause of irreversible vision loss. Current treatments are limited by suboptimal efficacy and significant complications, highlighting the need for new therapeutic strategies. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist primarily used for glycemic control and weight management, has recently shown potential anti-inflammatory effects. However, its role in AU remains unexplored. Here, we demonstrated that Ex-4 treatment effectively alleviated EAU symptoms. Our analysis revealed that Ex-4 partially reversed both the proportional changes and transcriptional alterations in immune cell populations during EAU. Bioinformatic analysis showed that Ex-4 suppressed the EAU-induced upregulation of PIM1 expression. Subsequent experiments revealed that Ex-4 restored the effector T (Teff) /regulatory T (Treg) cell balance via the suppression of the PIM1-protein kinase B (Akt)-Forkhead box O1 (FOXO1) pathway.These effects were further observed in patients with Vogt-Koyanagi-Harada disease (VKH), a human uveitis. Our study provides valuable insights into Ex-4- mediated immune modulation and highlights potential therapeutic targets for autoimmune uveitis.

Keywords

Autoimmune uveitis; Exendin-4; PIM1; Single-cell RNA sequencing.

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