Systemic semaglutide provides a mild vasoprotective and antineuroinflammatory effect in a rat model of ocular hypertensive glaucoma

Glaucoma is a neurodegenerative disease affecting retinal ganglion cells (RGCs), with a multifactorial genesis that includes inflammation and vascular dysfunction. Emerging evidence suggests that glucagon-like peptide 1 receptor agonist (GLP-1RAs) may serve as promising neuroprotective agents in glaucoma. In this study, we investigated the neuroprotective potential of the GLP-1RA semaglutide (SEM) in a rat model of ocular hypertension (OHT) induced by paramagnetic bead injections in Brown Norwegian rats. Rats were divided into four cohorts, two normotensive (NT) cohorts, and two OHT cohorts, treated with either SEM or saline (HBSS), which served as control. Systemic SEM or HBSS administration was initiated simultaneously with OHT induction. We observed that SEM administration seemed to delay the increase in intraocular pressure (IOP) associated with OHT. Although SEM administration did not improve RGC survival, it significantly improved astrocytic fractal dimension value and lacunarity. In conclusion, our findings suggest that GLP-1RAs may exert neuroprotective effects by delaying IOP elevation and preventing OHT-induced reactive astrocyte and vascular remodeling. These findings highlight the potential of GLP-1RAs for retinal neuroprotection, but further studies are needed to elucidate their applicability in glaucoma.