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REVIEW article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1618079

This article is part of the Research TopicOptimizing GLP-1 Receptor Agonist Use: Mechanisms, Clinical Applications, and Safety ProfilesView all 8 articles

Unlocking the Potential of GLP-1 Receptor Agonists in Ocular Therapeutics: From Molecular Pathways to Clinical Impact

Provisionally accepted
  • 1Department of Ophthalmology, Peking Union Medical College Hospital (CAMS), Beijing, China
  • 2Peking Union Medical College Hospital (CAMS), Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for diabetes and obesity, exhibit pleiotropic effects-including anti-inflammatory, antioxidant, and neuroprotective properties-that position them as transformative candidates for ocular therapeutics. Ocular diseases such as glaucoma and diabetic retinopathy (DR) are driven by multifactorial pathogenesis. Current therapies often target specific pathways or symptoms, and the potential effect of GLP-1RAs on the eye is still debated. The latest research and trials on the effect of GLP-1RAs in the eye were searched until April 2025, including thorough cellular studies, animal studies, and clinical observation surrounding glaucoma, diabetic retinopathy, and other ocular diseases. This review delineates the multifaceted mechanisms by which GLP-1RAs exert ocular benefits, including retinal ganglion cell (RGC) rescue via calcium channel and GABAergic modulation, mitochondrial protection through PINK1/Parkin-mediated mitophagy and ERK1/2-HDAC6 signaling, as well as potent anti-inflammatory effects via cytokine reduction and immune cell recruitment inhibition. Moreover, GLP-1RAs contribute to retinal remodeling by stabilizing vascular integrity and extracellular matrix homeostasis, and they display anti-angiogenic properties critical for mitigating neovascular complications. Clinical evidence underscores a reduced incidence of glaucoma and potential benefits in diabetic retinopathy. However, conflicting evidence highlights context-dependent risks, such as early DR worsening in poorly controlled glycemic states. In conclusion, this review synthesizes molecular insights and clinical evidence to underscore GLP-1RAs' potential as multi-targeted disease-modifying agents, urging further research to translate preclinical promise into safe, effective ocular therapies.

Keywords: glucagon-like peptide-1 receptor agonists, ocular diseases, Glaucoma, Diabetic Retinopathy, Mechanism

Received: 28 Apr 2025; Accepted: 08 Jul 2025.

Copyright: © 2025 Xie, Yang, Tian and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Youxin Chen, Department of Ophthalmology, Peking Union Medical College Hospital (CAMS), Beijing, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.