Immunosenescence in Uveitis: From Mechanistic Insights to Therapeutic Implications.

Authors

Yifei Wu, Yaru Zou, Mingming Yang, Wendong Gu, Zizhen Ye, Jiaxin Deng, Kyoko Ohno-Matsui, Koju Kamoi

Published in

Ageing research reviews. Pages 103381. Sep 22, 2026. Epub Sep 22, 2026.

Abstract

Immunosenescence-the age-associated remodeling of the immune system-has emerged as a potential modifier of chronic inflammatory disease. This review examines the evidence that immunosenescence may contribute to the chronicity, refractoriness, and therapeutic heterogeneity of uveitis, and considers the clinical and translational implications of this framework. It first outlines the features of immune aging, including thymic involution, contraction of the naïve T cell pool, accumulation of memory and terminally differentiated populations, and a chronic low-grade inflammatory state (inflammaging), and discusses signaling pathways that have been associated with these processes, including AMPK-mTOR, NF-κB, cGAS-STING, and JAK-STAT. It then evaluates three complementary but unequal lines of evidence relevant to uveitis: direct human observations from peripheral blood and intraocular fluids, mechanistic support from experimental models, and contextual inference from age-associated ocular disorders. Collectively, these data suggest that age-related immune remodeling may promote breakdown of ocular immune privilege, blood-retinal barrier dysfunction, persistent cytokine signaling, and incomplete response to conventional therapy in selected uveitis phenotypes. Finally, this review discusses therapeutic implications, including Treg enhancement, cytokine-directed approaches, and advanced drug delivery, while emphasizing that direct evidence of immune rejuvenation in human uveitis remains lacking. Ageing does not simply amplify ocular inflammation; it may attenuate selected acute immune responses while impairing resolution and tissue resilience, with effects that depend on disease context. By bridging geroscience and ocular immunology, this review offers a translational framework for understanding refractory intraocular inflammation and highlights future priorities for biomarker development, patient stratification, and precision medicine in uveitis.

PMID:
42772576
Bibliographic data and abstract were imported from PubMed on 23 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.