Does semaglutide provide neuroprotection in models of glaucoma?

Abstract

Listen

Translate article

Aims/Purpose: Semaglutide, a prominent member of the GLP‐1 receptor agonists, has gained considerable attention for its efficacy in managing type 2 diabetes and obesity. However, emerging evidence expand its therapeutic potentials far beyond glycemic control and weight management. Preclinical studies indicate that through anti‐inflammatory, anti‐oxidative and anti‐apoptotic effects GLP‐1 receptor agonists offer a promising new approach to neuroprotection in neurodegenerative conditions. In this study, we assess the neuroprotective properties of semaglutide in animal models of retinal neurodegeneration.Methods: C57BL/6 mice were treated with semaglutide (5mg/kg) for a week and then received intravitreal injections of 1% DMSO or the Complex I inhibitor rotenone. Retinas were isolated as either retinal explants or flat mounts. Retinal ganglion cell (RGC) degeneration was assessed using immunofluorescence and metabolic effects through stable isotope labeling (13C) and gas chromatography‐mass spectrometry (GC‐MS). We furthermore induced ocular hypertension through injection of magnetic beads into the anterior chamber of Brown Norway rats and initiated semaglutide treatment simultaneously; naïve rats served as controls. In the rats, RGC degeneration and glial cell changes were assessed through immunofluorescence.Results: We observed increased RGC survival upon treatment with semaglutide in rotenone insulted retinas. Furthermore, we found an increased metabolism of glucose in retinas exposed to semaglutide, and a compromised metabolism in retinas exposed to rotenone. We found no increased RGC survival in the rats, but a decreased macroglia activation upon treatment with semaglutide.Conclusions: Our results confirm the potential neuroprotective role of semaglutide involving metabolic and inflammatory pathways. Further studies are needed to elucidate the potential clinical implications of the current findings.