Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Levels Are Differentially Elevated in Patients with Advanced Retinopathy of Prematurity

Abstract

Although the roles of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in angiogenesis are well described, the putative roles of these factors in retinopathy of prematurity (ROP) remain unknown. We evaluated VEGF and HGF protein levels in subretinal fluid of eyes with ROP, and expression of their corresponding receptors in retrolental membranes associated with stage 5 ROP. We examined subretinal fluid samples from eyes using rhegmatogenous retinal detachment as a control. VEGF and HGF were differentially elevated in eyes with ROP. In Stage 5 ROP (n ‫؍‬ 22), the mean VEGF and HGF levels were 14.77 ؎ 14.01 ng/ml and 16.56 ؎ 9.62 ng/ml, respectively. Interestingly, in patients with active stage 4 ROP, mean VEGF levels were highly elevated (44.16 ؎ 18.72 ng/ml), whereas mean HGF levels remained very low (4.77 ؎ 2.50 ng/ml). Angiogenesis plays an essential role not only in normal physiology, but also in many pathological conditions such as proliferative diabetic retinopathy, age-related macular degeneration, and tumor growth.

Non-Paralleled Increase of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor in the Eyes with Angiogenic and Nonangiogenic Fibroproliferation

“…In contrast, high concentrations of HGF were noticed in the eyes of patients with a higher grade of PVR [27]. In eyes with retinopathy of prematurity (ROP), VEGF concentrations in the subretinal fluid were significnatly higher in stage 4 with active angiogenesis than in stage 5 with more fibroproliferation, while significantly higher concentrations of HGF were found in stage 5 [28]. These findings indicate HGF may be more important in pathological fibroproliferative processes in the eye than in angiogenesis.…”

Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures

“…VEGF is known to be significantly elevated in the ocular fluid of diabetic patients but has also been shown to be decreased in ischemic nonretinal tissues. [27][28][29][30] Because VEGF has a stimulatory effect on EPC proliferation and is a potent stimulator of vasculogenesis, 31 unique retinal pathways for VEGF regulation may be sufficient to overcome EPC dysfunction resulting in diabetic retinopathy. Work currently underway in our laboratory supports this notion and demonstrates that nonretinal VEGF administration reverses impaired wound healing in diabetic animal models by mobilizing and attracting bone marrow-derived EPCs (unpublished data).…”

Delayed onset atypical vitreoretinal traction band formation after an intravitreal injection of bevacizumab in stage 3 retinopathy of prematurity

“…VEGF is obviously one of the most important molecules in the development of oxygen-induced retinopathy mouse model 1,2 and elevated intraocular concentration of VEGF is consistently documented in ROP patients. 3,4 For these reasons, bevacizumab has been applicated in limited ROP cases and several clinical articles that report the efficacy and complications of the bevacizumab treatment for ROP were issued recently. Bevacizumab not only had been used as a salvage treatment in progressive cases after conventional laser photocoagulation, 5-8 but also had been applied simultaneously with retinal photocoagulation.…”