Topical and systemic GLP-1R agonist administration both rescue retinal ganglion cells in hypertensive glaucoma

Front Cell Neurosci. 2023 Jun 9:17:1156829. doi: 10.3389/fncel.2023.1156829. eCollection 2023.

Abstract

Glaucomatous neurodegeneration, a blinding disease affecting millions worldwide, has a need for the exploration of new and effective therapies. Previously, the glucagon-like peptide-1 receptor (GLP-1R) agonist NLY01 was shown to reduce microglia/macrophage activation, rescuing retinal ganglion cells after IOP elevation in an animal model of glaucoma. GLP-1R agonist use is also associated with a reduced risk for glaucoma in patients with diabetes. In this study, we demonstrate that several commercially available GLP-1R agonists, administered either systemically or topically, hold protective potential in a mouse model of hypertensive glaucoma. Further, the resulting neuroprotection likely occurs through the same pathways previously shown for NLY01. This work contributes to a growing body of evidence suggesting that GLP-1R agonists represent a viable therapeutic option for glaucoma.

Keywords: glaucoma; glucagon-like peptide-1 receptor agonist; macrophage; microglia; neuroinflammation; neuroprotection; optic nerve (ON); retinal ganglion cell (RGC).