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

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.

[1]  Jia Yin,et al.  Growth factors and corneal epithelial wound healing , 2010, Brain Research Bulletin.

[2]  L. Golub,et al.  Effect of Doxycycline Hyclate on Corneal Epithelial Wound Healing in the Rabbit Alkali-Burn Model: Preliminary Observations , 1993, Cornea.

[3]  R. D'Amato,et al.  Thalidomide is an inhibitor of angiogenesis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[4]  H. Bazan,et al.  Increased platelet-activating factor receptor gene expression by corneal epithelial wound healing. , 2000, Investigative ophthalmology & visual science.

[5]  A. Leong,et al.  A comparative study of cell proliferation markers in breast carcinomas , 1995, Clinical molecular pathology.

[6]  Fen Chen,et al.  Enhanced functional properties of corneal epithelial cells by coculture with embryonic stem cells via the integrin β1-FAK-PI3K/Akt pathway. , 2011, The international journal of biochemistry & cell biology.

[7]  Jingtai Cao,et al.  VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. , 2004, The Journal of clinical investigation.

[8]  R. Tripathi,et al.  Prospects for epidermal growth factor in the management of corneal disorders. , 1990, Survey of ophthalmology.

[9]  B. Lindström,et al.  Hyaluronate in healing of corneal alkali wound in the rabbit. , 1989, Experimental eye research.

[10]  Y. Fang,et al.  Implantation of Hydroxyapatite–Titanium Corneal Implants in Rat Cornea , 2011, Cornea.

[11]  Rafael Sirera,et al.  Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood. , 2006, Lung cancer.

[12]  H. Sheardown,et al.  Growth factors in the anterior segment: role in tissue maintenance, wound healing and ocular pathology. , 2004, Experimental eye research.

[13]  J. Ge,et al.  Establishment of a corneal epithelial cell line spontaneously derived from human limbal cells. , 2007, Experimental eye research.

[14]  Yu-Feng Yao,et al.  Reactive oxygen species (ROS) are essential mediators in epidermal growth factor (EGF)-stimulated corneal epithelial cell proliferation, adhesion, migration, and wound healing. , 2009, Experimental eye research.

[15]  T. Chikama,et al.  Cell–matrix and cell–cell interactions during corneal epithelial wound healing , 2003, Progress in Retinal and Eye Research.

[16]  J. Capó-Aponte,et al.  Epidermal growth factor receptor transactivation by the cannabinoid receptor (CB1) and transient receptor potential vanilloid 1 (TRPV1) induces differential responses in corneal epithelial cells. , 2010, Experimental eye research.

[17]  Steven E. Wilson,et al.  Biomechanics and wound healing in the cornea. , 2006, Experimental eye research.

[18]  M. Ohji,et al.  Transforming growth factor-β stimulates collagen and fibronectin synthesis by human corneal stromal fibroblasts in vitro , 1993 .

[19]  W. Su,et al.  The effect of doxycycline temperature-sensitive hydrogel on inhibiting the corneal neovascularization induced by BFGF in rats , 2011, Graefe's Archive for Clinical and Experimental Ophthalmology.

[20]  D. Azar,et al.  Neostatin‐7 regulates bFGF‐induced corneal lymphangiogenesis , 2008, FEBS letters.

[21]  S. Higashiyama,et al.  Corneal epithelial wound healing impaired in keratinocyte-specific HB-EGF-deficient mice in vivo and in vitro. , 2010, Investigative ophthalmology & visual science.

[22]  S. Priglinger,et al.  Role of tissue growth factors in aqueous humor homeostasis , 2001, Current opinion in ophthalmology.

[23]  D. Azar.  Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis). , 2006, Transactions of the American Ophthalmological Society.

[24]  D. Azar,et al.  Novel aspects of corneal angiogenic and lymphangiogenic privilege , 2010, Progress in Retinal and Eye Research.

[25]  J. Chung,et al.  Effect of topically applied Na-hyaluronan on experimental corneal alkali wound healing. , 1996, Korean journal of ophthalmology : KJO.

[26]  C. Sotozono,et al.  Growth factors: importance in wound healing and maintenance of transparency of the cornea , 2000, Progress in Retinal and Eye Research.

[27]  C. Hecquet,et al.  Effects of acidic and basic fibroblast growth factors on the proliferation of rabbit corneal cells. , 1990, Current eye research.

[28]  L. Furcht,et al.  Epidermal growth factor stimulates integrin-mediated cell migration of cultured human corneal epithelial cells on fibronectin and arginine-glycine-aspartic acid peptide. , 1995, Investigative ophthalmology & visual science.

[29]  M. Ding,et al.  Basic fibroblast growth factor stimulates epithelial cell growth and epithelial wound healing in canine corneas. , 2009, Veterinary ophthalmology.

[30]  P. Mulder,et al.  Influence of topical human epidermal growth factor on postkeratoplasty re-epithelialisation , 1997, The British journal of ophthalmology.

[31]  Y. Liu,et al.  Rapidly constructed scaffold-free cornea epithelial sheets for ocular surface reconstruction. , 2011, Tissue engineering. Part C, Methods.