Protective Effect of Granulocyte Colony Stimulating Factor on Human Retinal Endothelial Cell Injured by Oxidative Stress

Abstract

Purpose: : Granulocyte colony stimulating factor (G-CSF) has been shown to have direct protective effect in cerebral stroke model and light-induced retinal damage model. In the present study, we investigated whether G-CSF has protective effect on human retinal endothelial cell injured by oxidative stress and inhibits pathological neovascularization in the mouse model of retinopathy of prematurity.

Methods: : Human endothelial cells were exposed H₂O₂ with or without G-CSF. Apoptotic cells were detected with Annexin V staining. Oxygen induced retinopathy (OIR) model of new born mice was used as a retinal angiogenesis model. G-CSF or vehicle was injected systemically for consecutive 5 days prior to and during oxygen exposure (between P6 and P10).To quantify the area of retinal neovasculareization and vasoobliteration, we stained retinal flat mount with collagen IV at P17. The neuroprotective effect was evaluated through electroretinography (ERG) and retinal histology at P30.

Results: : G-CSF decreased apoptotic cells by oxidative stress. Further, in mice model, injection of G-CSF inhibits retinal pathological neovascularization and decrease the area of vasoobliteration. The outer plexiform layer thickness was limited reduction, and an electroretinogram confirmed the preservation of wave amplitudes in early G-CSF-treated mice.

Conclusions: : G-CSF protect retinal endothelial cells directly from oxidative stress and inhibits pathological neovascularization and protects retinal function and structural damage in the mouse of ROP. These findings may lead to a novel treatment strategy for ischemic diseases of the retina.

Keywords: apoptosis/cell death • retinopathy of prematurity • retinal neovascularization