Ethyl pyruvate inhibits retinal pathogenic neovascularization by downregulating HMGB1 expression

Area of Science:

• Ophthalmology
• Molecular Biology
• Pharmacology

Background:

• Retinal pathogenic angiogenesis contributes to vision-threatening conditions like diabetic retinopathy.
• High-mobility group box-1 (HMGB1) protein plays a role in abnormal blood vessel growth in the retina.
• Oxygen-induced retinopathy (OIR) is a key animal model for studying proliferative ischemic retinopathies.

Purpose of the Study:

• To investigate the pathogenic role of HMGB1 in retinal angiogenesis.
• To evaluate the inhibitory effect of ethyl pyruvate (EP) on retinal neovascularization in OIR mice.
• To determine if EP affects HMGB1 expression in OIR.

Main Methods:

• Established the OIR mouse model by exposing mice to 75% oxygen from postnatal day 7 to 11.
• Administered intraperitoneal injections of ethyl pyruvate (50 mg/kg or 100 mg/kg) for five days.
• Assessed retinal nonperfused areas and neovascular tufts using fluorescein isothiocyanate-dextran perfusion and flat-mounted retinas at postnatal day 17.

Main Results:

• Ethyl pyruvate treatment significantly reduced the nonperfused retinal area in OIR mice.
• EP administration markedly decreased the number of retinal neovascular tufts.
• EP inhibited the overexpression of HMGB1 in the retinas of OIR mice.

Conclusions:

• Ethyl pyruvate demonstrates potential as a therapeutic agent for preventing retinal neovascularization.
• Inhibition of HMGB1 expression by EP is a key mechanism in its anti-angiogenic effect.
• These findings support EP as an innovative pharmaceutical candidate for treating proliferative retinopathies.