Hepatocyte growth factor (HGF) stimulates ocular neovascularization and vascular leakage and may contribute to NV and macular edema in ischemic retinopathies.

Abstract

Purpose : To investigate the effects of hepatocyte growth factor (HGF) on retinal and choroidal vasculature and its role of in ocular neovascularization and vascular leakage.

Methods : HGF mRNA was measured in retinas of mice with oxygen-induced ischemic retinopathy (OIR) and controls by qRT-PCR. At P12, mice with OIR were given an intravitreous injection of anti c-Met (0.45μg) or HGF (0.5μg) in one eye and mouse IgG (0.45μg) or albumin (0.5μg) in the other eye; and at P17 the area of NV was measured. Adult mice were given an intravitreous injection of anti-c-Met (0.45μg) or HGF (0.5μg) in one eye and mouse IgG (0.45μg) or albumin (0.5μg) in the other; and then had laser-induced rupture of Bruch’s membrane in each eye. After 7 days the area of choroidal NV was measured. Adult mice had injection of HGF (0.5μg) or VEGF (0.5μg) in one eye and mouse IgG in the other and after 1 or 3 days the amount of serum albumin in the retina was measured by ELISA and western blot.

Results : HGF mRNA was significantly increased in retinas from OIR mice compared to those from room air controls at P15 (1446±154 vs 991±72 HGF transcripts/10⁶ cyclophillin A transcripts, p= 0.02) and P17 (1327±61 vs 1009±79 HGF transcripts/10⁶ cyclophillin A transcripts, p=0.007). The area of retinal NV in OIR mice was significantly reduced in eyes injected with anti-c-Met compared with IgG (1.01±0.08 vs 1.39±0.11 mm², p=0.007) and was significantly increased in eyes injected with HGF compared with albumin (2.31± 0.22 vs 1.56± 0.15 mm², p=0.01). The area of choroidal NV was not significantly decreased in eyes injected with anti-c-Met compared with IgG (0.012±0.001 vs 0.017±0.002 mm², p=0.14), but was significantly increased in eyes injected with HGF compared with albumin (0.026±0.006 vs 0.013±0.002 mm², p= 0.04). In normal mice, there was a significant increase in albumin in the retina at 1 and 3 days after injection of HGF; and was increased at 1, but not 3 days after injection of VEGF.

Conclusions : Expression of HGF is increased in ischemic retina and injection of HGF stimulates growth of retinal and choroidal NV and causes retinal vascular leakage. Inhibition of c-Met suppresses retinal, but not choroidal NV. These data suggest that HGF may contribute to NV and macular edema in eyes with ischemic retinopathy.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.