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

Jianhong Zhou, Xiangxiang Lin, Huiping Shang, Yutuo Zhu, Jinrun Chen, Mengyun Deng, Mali Dai, Dan Lin, Serhii Vakal, Yuqin Wang*, Xingyi Li*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

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.
Original languageEnglish
Article number114917
JournalBiochemical Pharmacology
Volume197
DOIs
Publication statusPublished - Mar 2022
MoE publication typeA1 Journal article-refereed

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