2. Academic Validation
  3. Ganciclovir attenuates the onset and progression of experimental autoimmune uveitis by inhibiting infiltration of Th17 and inflammatory cells into the retina

Ganciclovir attenuates the onset and progression of experimental autoimmune uveitis by inhibiting infiltration of Th17 and inflammatory cells into the retina

  • Biochem Pharmacol. 2022 Mar;197:114917. doi: 10.1016/j.bcp.2022.114917.
Jianhong Zhou 1,  Xiangxiang Lin 2,  Huiping Shang 1,  Yutuo Zhu 1,  Jinrun Chen 1,  Mengyun Deng 1,  Mali Dai 1,  Dan Lin 1,  Serhii Vakal 3,  Yuqin Wang 4,  Xingyi Li 5
Affiliations

Affiliations

  • 1 Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, China.
  • 2 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, First affiliated hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Structural Bioinformatics Laboratory, Biochemistry, Åbo Akademi University, Turku 20541, Finland.
  • 4 Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, China. Electronic address: wangyuqin@mail.eye.ac.cn.
  • 5 Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, China. Electronic address: lixingyi_1984@mail.eye.ac.cn.
PMID: 35041813 DOI: 10.1016/j.bcp.2022.114917
Abstract

Noninfectious (autoimmune and immune-mediated) uveitis is one of the primary diseases leading to blindness in the world. Due to the limitation of current first-line drugs for clinical uveitis, novel drugs and targets against uveitis are urgently needed. Ganciclovir (GCV), an FDA-approved Antiviral drug, is often used to treat cytomegalovirus-induced retinitis in clinical patients. Recently, GCV was found to suppress neuroinflammation via targeting STING signaling because the STING pathway plays a pivotal role in autoimmune diseases. However, until now, the effect of GCV on non-infectious uveitis has never been explored. In this work, using the rat experimental autoimmune uveitis (EAU) model, we first found STING to be highly expressed in infiltrating cells (CD68+, CD45+, and CD4+) and retinal glial cells (Iba1+ and GFAP+) of the immunized retina. More importantly, GCV treatment can significantly suppress the initiation and progression of EAU by inhibiting infiltration of Th17 and inflammatory cells into the retina. Mechanistically, we found that GCV could reverse the levels of pro-inflammatory factors (such as IL-1β) and chemokine-related factors (such as CXCR3), possibly via targeting the STING pathway. The present results suggest that GCV may be considered as a novel therapeutic strategy against human uveitis.

Keywords

EAU; Ganciclovir; Inflammatory cells; STING; Th17 cells.

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