Therapeutic effect of cilastatin administration in LPS-induced retinotoxicity

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection that leads to multi-organ dysfunction. While its impact on the central nervous system is increasingly recognized, its effects on the retina require further study. Herein, we aimed to determine if systemic LPS‑induced sepsis causes retinal damage and whether cilastatin (CIL) may attenuate this injury. For that purpose, twenty-eight male Wistar rats were administered with intraperitoneal LPS (10 mg/kg) or vehicle, combined with CIL (150 mg/kg) or vehicle. After 24 h, body weight and renal function were recorded, and eyes were harvested. Immunohistochemical analysis was performed to evaluate RGCs (Brn3a), macroglia (GFAP), and microglia (Iba1). LPS caused body weight loss and renal dysfunction. In the retina, LPS triggered a reduction in Brn3a⁺ RGCs near the optic nerve (ON), together with an increase in GFAP and Iba1 expression, indicating a glial activation response and a shift to a reactive, horizontally migratory morphotype. CIL treatment attenuated these systemic and retinal alterations, preserving RGC counts and limiting glial reactivity, particularly in the peri-optic nerve regions where LPS-induced damage was most severe. Our results demonstrate that LPS-induced sepsis in male Wistar rats triggers retinal glial activation and neuronal injury. These findings support the further investigation of CIL as a potential protective agent in the context of systemic inflammation.