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

Area of Science:

• Ophthalmology
• Cell Biology
• Pharmacology

Background:

• Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults.
• The inflammatory response of retinal Müller cells (RMCs) is a key factor in DR pathogenesis.
• Heparanase inhibitors, like PG545, exhibit proautophagic and anti-inflammatory properties.

Purpose of the Study:

• To investigate the therapeutic potential of PG545 in mitigating diabetic retinopathy.
• To elucidate the mechanisms by which PG545 affects RMCs and inflammation in DR.

Main Methods:

• In vivo studies using a mouse model of diabetes to assess the effects of PG545 on body weight, blood glucose, and retinal structural changes.
• In vitro experiments using high glucose-induced primary adult mouse RMCs to evaluate PG545's impact on autophagy and inflammatory markers.

Main Results:

• PG545 administration (20 mg/kg/d) reduced diabetes-induced body weight gain and fasting blood glucose levels in mice.
• PG545 treatment preserved retinal thickness and reduced microaneurysm formation.
• In vitro, PG545 promoted autophagy and downregulated the inflammatory response in RMCs exposed to high glucose.

Conclusions:

• PG545 effectively mitigates diabetic retinopathy in a mouse model.
• The mechanism involves PG545-induced autophagy in RMCs, leading to the inhibition of inflammatory responses.
• PG545 represents a promising therapeutic agent for diabetic retinopathy by targeting RMC autophagy and inflammation.