PG545 alleviates diabetic retinopathy by promoting retinal Müller cell autophagy to inhibit the inflammatory response

Abstract Diabetic retinopathy (DR), a major cause of blindness in working-age people, is attributed to the inflammatory response of retinal Muller cells (RMCs). The heparanase inhibitor PG545 plays proautophagic and anti-inflammatory roles. Intraperitoneal injection of PG545 at a dose of 20 mg/kg/d clearly reduced diabetes-induced body weight changes and fasting blood glucose levels in mice. PG545 also mitigated the reduction in retinal thickness and the formation of microaneurysms by promoting autophagy to inhibit the inflammatory response. In vitro, PG545 stimulated autophagy to downregulate the inflammatory response in high glucose-induced primary adult mouse RMCs. These data suggest that PG545 mitigates DR by promoting RMC autophagy to inhibit the inflammatory response.