2. Academic Validation
  3. Inhibition of RORγt suppresses both retinal and choroidal neovascularization in mice

Inhibition of RORγt suppresses both retinal and choroidal neovascularization in mice

  • Exp Eye Res. 2025 Aug 15:260:110573. doi: 10.1016/j.exer.2025.110573.
Yujuan Cai 1,  Siyu Jiang 2,  Yue Sun 2,  Nyamjargal Nyambayar 2,  Ruijie Lin 3,  Yanji Zhu 4,  Xiuping Chen 5,  Bing Xie 6
Affiliations

Affiliations

  • 1 Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, 750002, China; Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2 Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 3 Crean Lutheran High School, 12500 Sand Canyon Ave, Irvine, CA, 92618, USA.
  • 4 Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: yanji_zhu@126.com.
  • 5 Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 200025, China. Electronic address: Chen.xiuping@zs-hospital.sh.cn.
  • 6 Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: xb10937@rjh.com.cn.
PMID: 40819785 DOI: 10.1016/j.exer.2025.110573
Abstract

Retinal and choroidal neovascularization (RNV and CNV) are critical pathological features of vision-threatening ocular disorders. This study investigated the role of retinoic acid receptor-related Orphan Receptor γt (RORγt) in the regulation of RNV and CNV formation using oxygen-induced retinopathy (OIR) and CNV mouse models, and explored its underlying mechanisms. We demonstrated that RORγt expression was significantly elevated in retinal tissues of both models, co-localizing with IL-23 Receptor (IL-23R) and T-cell receptor γδ (TCRγδ), indicating its primary expression in Th17 and γδT cells. Pharmacological inhibition of RORγt with GSK805 effectively reduces pathological NV and leakage, as evidenced by decreased retinal NV areas, vaso-obliteration areas and Evans blue extravasations in the OIR model and reduced vascular leakage and CNV areas in the CNV model. Additionally, GSK805 treatment downregulated pro-inflammatory cytokines (IL-22 and IL-17A), angiogenic factors (angiopoietin 2, PDGF-B, and PDGFR-β), and inflammasome components (NLRP3 and ASC), while modulating macrophage polarization by reducing M1 markers and increasing M2 markers. These findings reveal that RORγt plays a supportive role in NV by influencing key inflammatory and angiogenic pathways, suggesting that RORγt inhibition may represent a promising therapeutic strategy for NV-related retinal diseases.

Keywords

Choroidal neovascularization; RORγt; Retinal neovascularization.

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