EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.

Exploring the Mechanism of Action Compound‐Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

“…After the specific binding of PDR, it plays a certain role in the formation and development of PDR in the form of autocrine or paracrine. Research from Ju et al pointed out that EGFR in the DR model seriously promoted retinal dysfunction, damage of retinal structure and mitochondrial structure in retinal vessels and retinal vascular abnormalities (including neovascularization) in diabetic mice [ 28 ].…”

Thermostable small-molecule inhibitor of angiogenesis and vascular permeability that suppresses a pERK-FosB/ΔFosB–VCAM-1 axis

“…2C and fig. S3A), where CD31 is expressed after laser injury (30). BT2 also inhibited the inducible expression of VEGF-A 165 ( Fig.…”

In Vitro Evaluation of the Neuroprotective Effect of Panax notoginseng Saponins by Activating the EGFR/PI3K/AKT Pathway

“…After treatment with PNS, cell viability was significantly elevated compared with the model group, and the effect of PNS was weakened when combined with AG1478. AG1478 is a specific inhibitor of EGFR [ 41 , 42 ] and abolished the neuroprotective effects of PNS. Obviously, the cell survival rate when AG1478 was used alone was significantly lower than that of the model group.…”