Comparative Study of the Effects of Recombinant Human Epidermal Growth Factor and Basic Fibroblast Growth Factor on Corneal Epithelial Wound Healing and Neovascularization in vivo and in vitro

Abstract

Purpose: This study was undertaken to investigate the effects of recombinant human epidermal growth factor (rhEGF) and basic fibroblast growth factor (bFGF) on corneal wound healing and neovascularization (CNV). Methods: The positive effects of 10 ng/ml rhEGF and bFGF on the proliferation of corneal epithelial cells (SD-HCEC1s), rabbit keratocyte cells (RKCs) and human umbilical vein endothelial cells (HUVECs) as well as the effects on the migration capacity on HUVECs were observed. An animal central corneal wound and CNV model was established in rabbits. One eye of each group was chosen randomly for topical administration of rhEGF, bFGF or normal saline, and variability in the area of corneal epithelial wound healing and CNV was observed. Results: The optimal concentration of rhEGF and bFGF for the proliferation of corneal epithelial cells was 10 ng/ml. The promotive effect of 10 ng/ml rhEGF on the proliferation of RKCs and HUVECs was less than that of 10 ng/ml bFGF. In the animal experiment, the healing rate of the corneal epithelium in the rhEGF group was better than in the other groups on day 1. On day 3, the healing rates of the 3 groups were nearly equal. The CNV area in the rhEGF group was less than that of the bFGF group. Conclusions: rhEGF and bFGF both had promotive effects on corneal epithelial wound healing, but rhEGF had a weaker promotive effect on CNV than bFGF. With long-term application of growth factor drugs, rhEGF is suggested for lessening the growth of CNV.

CXCR7/CXCR4/CXCL12 Axis Regulates the Proliferation, Migration, Survival and Tube Formation of Choroid-Retinal Endothelial Cells

“…Very recent studies showed that the application of growth factors could suppress CNV in animal models [14,15]. In the present study, we developed a different approach by employing RNAi-mediated knockdown of CXCR4 and CXCR7 in RF/6A cells.…”

Moist exposed burn ointment promotes cutaneous excisional wound healing in rats involving VEGF and bFGF

“…Increases in the number of fibroblasts primarily arise due to the proliferation of resident fibroblasts in response to growth factors, including bFGF, and fibroblasts migrating from the surrounding connective tissue into the wound site (40). It was observed that recombinant bFGF accelerates the wound healing process (14,41), thus, rb-bFGF was used as a positive control for MEBO. In the current study, rb-bFGF promoted the formation of granulation tissue, increased neovascularization and the number of fibroblasts in the granulation tissue, and reduced the time of wound healing, which were all consistent with the effects of MEBO.…”

“…In the current study, rb-bFGF promoted the formation of granulation tissue, increased neovascularization and the number of fibroblasts in the granulation tissue, and reduced the time of wound healing, which were all consistent with the effects of MEBO. It is generally accepted that VEGF induces endothelial cell proliferation and migration, promotes vascular permeability and angiogenesis, increases collagen deposition (5,(9)(10)(11), and that bFGF mediates angiogenesis, promotes the proliferation and migration of endothelial cells and fibroblasts proliferate and migration (12)(13)(14)(15)42). Therefore, it was inferred that MEBO promotion of wound healing in rats involves growth factors, including VEGF and bFGF.…”

“…VEGF and bFGF, however, are decreased in delayed cutaneous wounds, including diabetic wounds and chronic ulcers (17)(18)(19). Inhibition of VEGF and bFGF by neutralizing antibodies results in a decrease in the migration of fibroblasts and a delay in wound healing (20), while treatment with recombinant bFGF and VEGF, or overexpression of VEGF accelerates wound healing (14,21,22). Therefore, it is a potentially clinically beneficial to increase the levels of VEGF and bFGF in cutaneous wounds, particularly in delayed wound healing.…”

“…In addition, VEGF promotes epithelialization and collagen deposition in the wound (11). FGF-2, known as bFGF, is a member of a large FGF family and induces angiogenesis, endothelial cell and fibroblast proliferation, and wound healing (12)(13)(14). Recent data indicated that bFGF-mediated angiogenesis refers to endothelial cell proliferation, migration and tube formation by activating c-Jun N-terminal kinase/stress-activated protein kinase signaling (15).…”