Abstract

Retinal pathogenic angiogenesis in the eyes is a causative factor in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. This study was designed to examine the pathogenic role of the high-mobility group box-1 (HMGB1) protein and the inhibitory effect of ethyl pyruvate (EP), a well-known antioxidant substance, in retinal pathogenic angiogenesis in mice with oxygen-induced retinopathy (OIR), one of the animal models of proliferative ischemic retinopathy. The OIR mouse model was used for our in vivo studies. The mice were exposed to 75% oxygen from postnatal day 7 (P7) to P11, after which the mice were brought to room air and intraperitoneally injected with EP (50 mg/kg, or 100 mg/kg) for five days. At P17, the mice were perfused with fluorescein isothiocyanate-dextran, and flat-mounted retinas were used to measure nonperfused and neovascular tufts. In OIR mice, an intraperitoneal injection of EP reduced the nonperfused retinal area in the treatment group and significantly reduced the retinal neovascular tufts. In addition, EP inhibited the overexpression of HMGB1 in the retinas of OIR mice. These data suggest that EP could serve as an innovative pharmaceutical agent to prevent retinal neovascularization through inhibiting HMGB1 expression.

Highlights

  • Angiogenesis, the formation of new vessels from existing vessels, plays an important role in pathological conditions in various organs [1]

  • We examined whether ethyl pyruvate (EP) has a preventive effect against pathological retinal neovascularization and inhibits high-mobility group box-1 (HMGB1) expression in a mouse model of oxygen-induced retinopathy (OIR)

  • Retinal neovascularization (RNV) is a major cause of blindness associated with ischemic retinopathy [2, 23]

Read more

Summary

Introduction

Angiogenesis, the formation of new vessels from existing vessels, plays an important role in pathological conditions in various organs [1]. Pathological angiogenesis in the eye is the most common cause of blindness in all age groups. Retinopathy of prematurity (ROP) occurs in children, diabetic retinopathy (DR) in young adults, and age-related macular degeneration (AMD) in the elderly [2]. It is important to understand the mechanism of underlying pathological neovascularization to identify new targets to treat these diseases. Some evidence indicates that chronic inflammation is implicated in the pathogenesis of retinal neovascularization [4, 5]. The relationship between chronic inflammation and pathogenic angiogenesis is widely accepted [6]. The high-mobility group box-1 (HMGB1) protein was initially discovered as a nuclear chromatin-binding protein that stabilizes nucleosome formation and facilitates transcription

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call