Suvorexant protects db/db mice from diabetic ocular complications by reducing retinal inflammation and improving glucose.

Diabetic ocular complications, including diabetic retinopathy, are a leading cause of vision loss in patients with Type 2 Diabetes (T2D). Current treatments primarily focus on glycemic control or direct ocular interventions, often failing to fully prevent or reverse vision impairment. Orexins, hypothalamic neuropeptides, are known for their role in wakefulness but also influence glucose homeostasis. Suvorexant, a dual orexin receptor antagonist, is approved for insomnia and has shown promise in lowering blood glucose in rodent studies, suggesting a potential broader therapeutic utility beyond sleep regulation.

Male db/db mice (a model for T2D) were treated daily with Suvorexant (30 mg/kg, intraperitoneal) or vehicle for 12 weeks. Visual assessments included electroretinogram to measure retinal function, optomotor response test for visual acuity, and fluorescein angiography to evaluate retinal vascular parameters. Glucose and insulin tolerance tests assessed glycemic control. Post-euthanasia, retinas were isolated for qPCR to quantify gene expression and immunofluorescence staining to analyze protein levels.

Suvorexant treatment significantly improved visual acuity and retinal vascular parameters, including a reduction in avascular areas and an increase in vascular areas. The study observed a decrease in scotopic a-wave and b-wave amplitudes in suvorexant-treated mice, alongside an increased b-wave implicit time. Molecular analysis revealed that suvorexant downregulated mRNA expression of phospholipase C γ1 and protein kinase C beta (PKCβ), as well as key inflammatory markers tumor necrosis factor-α (Tnf-a) and interleukin 1β (Il-1b). Consistent with these mRNA changes, immunofluorescence studies of retinal transverse sections showed reduced protein expression of PKCβ and CD45.