Neuroprotective Effects of Glucagon-like Peptide-1/glucagon-like Peptide-1 Receptor Agonists on Neurodegenerative Eye Diseases and their Molecular Mechanisms: A Recent Update.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a novel class of glucose-lowering drugs, specifically bind to the glucagon-like peptide-1 receptor and substantially improve glycemic control by mimicking the physiological effects of endogenous glucagon-like peptide-1 (GLP-1). Recent studies have shown multiple beneficial effects of GLP-1 and GLP-1RAs, including anti-inflammatory, antioxidant, and neuroprotective effects, indicating their potential therapeutic applications in treating neurodegenerative diseases. Notably, several ocular disorders, including diabetic retinopathy, glaucoma, age-related macular degeneration, and dry eye disease, also exhibit neurodegeneration-related pathophysiological changes. Hence, it is critical to explore new therapeutic strategies to address the clinical challenges posed by these neurodegenerative ocular diseases. Given this background, we conducted a review of recent preclinical and clinical studies to update and summarize (1) the therapeutic potential of GLP-1/GLP-1RAs for neurodegenerative ocular diseases, (2) clinical evidence supporting the neuroprotective effects of GLP-1/GLP-1RAs in these ocular diseases, and (3) the molecular mechanisms underlying the neuroprotective effects of GLP-1/GLP-1RAs on ocular neural cells, including inflammatory and oxidative stress response inhibition and Ca2+ homeostasis regulation. This review aims to provide a theoretical foundation and research outlook for extending the application of GLP-1RAs to treat neurodegenerative ocular diseases.