Ethyl Pyruvate Inhibits Retinal Pathogenic Neovascularization by Downregulating HMGB1 Expression

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.

HMGB1 may act via RAGE to promote angiogenesis in the later phase after intracerebral hemorrhage

“…For example, EP down-regulated activation of the proinflammatory transcription factor, as well as the expression of several proinflammatory proteins (Su et al, 2011;Luan et al, 2013). But some studies demonstrated that EP could decrease the expression of HMGB1 (Su et al, 2011;Lee et al, 2013;Cheng et al, 2014). In our study the administration of EP significantly reduced ICH-induced upregulation of the expression of HMGB1, RAGE and VEGF, as well as the ICHinduced increase in vessel density.…”

“…Previous studies also indicated that EP could decrease the expression of HMGB1 and secretion from the nucleus into the cytoplasm in other models (Su et al, 2011;Lee et al, 2013;Cheng et al, 2014).…”

Sipjeondaebo-Tang, a Traditional Herbal Formula, Inhibits Retinal Neovascularization in a Mouse Model of Oxygen-Induced Retinopathy

“…The value of 50% inhibition concentration (IC 50 ) was calculated from the dose inhibition curve. attenuated retinal neovascularization in OIR mice (Lee et al 2013). Therefore, it is suggested that the inhibition of retinal neovascularization by SDT may be due to synergic effects of paeoniflorin and glycyrrhizin.…”

Anti-glycation and anti-angiogenic activities of 5′-methoxybiphenyl-3,4,3′-triol, a novel phytochemical component of Osteomeles schwerinae

“…OIR was induced in mouse (C57BL/6) according to a method by Smith et al (1994) and that was previously described (Lee et al, 2013). On postnatal day 12 (P12), after the mice were exposed to 757 2% oxygen for 5 days (P7-P12), they were randomly assigned to four groups: saline treated OIR mice, OIR mice treated K24-10 (10 mg/kg/day), K24-50 (50 mg/kg/day), K24-100 (100 mg/kg/ day).…”