Biochemical and Biophysical Research Communications, Vol.508, No.1, 130-137, 2019
Overexpressing kringle 1 domain of hepatocyte growth factor with adeno-associated virus inhibits the pathological retinal neovascularization in an oxygen-induced retinopathy mouse model
Current clinical treatments for ocular neovascularization are characterized by high possibility of damaging healthy tissues and high recurrence rates. It is necessary to develop new treatment methods to control neovascularization with a stable and effective effect. Kringle1 domain of hepatocyte growth factor (HGFK1) has anti-angiogenesis activity. Here, we established oxygen-induced retinopathy (OIR) model to study if using adeno-associated virus (AAV) as a delivery system to overexpression HGFKI in retinal cells could benefit retinal neovascularization. We show that, overexpressed exogenous gene was mainly expressed in the inner and outer nuclear layer of the retina. Compared with control mice, the mice pretreated with rAAV-HGFK1 at P3 showed relatively normal vascular branches examined by fluorescence fundus angiography. Subsequent H&E staining and immunohistochemical staining of CD31 of the eye tissue sections showed that the mice received rAAV-HGFK1 had a relatively normal distribution of vascular endothelial cells. Additionally, immunohistochemical staining indicated a lower expression of VEGF in the eye tissues of rAAV-HGFK1 treated OIR mice. Further in vitro studies showed that HGFKI could inhibit the proliferation but promote the apoptosis of bovine retinal microvascular endothelial cells (BRECs) under the presence of VEGF. Moreover, HGFKI could inhibit VEGF induced ERK activation but promote p38 activation in BRECs. Therefore, we propose that intravitreal injection of rAAV-HGFK1 might be used to improve the retinal neovascularization and HGFKI may function through regulating VEGF signaling pathway to inhibit neovascularization. (C) 2018 Elsevier Inc. All rights reserved.