Human recombinant epidermal growth factor in experimental corneal wound healing.
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Human recombinant epidermal growth factor (hEGF) was evaluated in various corneal wound healing models in the rabbit. Human EGF accelerated epithelial wound healing in corneal reepithelialization, anterior-keratectomy, and alkali-burn models at concentrations of 10-500 micrograms/ml given four times daily (qid). In the corneal reepithelialization model, 100 micrograms/ml of hEGF qid produced a 45% increase in the wound-healing rate compared with control (0.13 versus 0.09 mm/hr) with a similar response at 500 micrograms/ml qid. In the anterior-keratectomy model, 500 micrograms/ml of hEGF qid accelerated healing by 40% (0.07 versus 0.05 mm/hr), although the 100 micrograms/ml dose was not active in this model, and 1 microgram/ml of hEGF actually slowed the healing rate. In the alkali-burn model, 10 and 100 micrograms/ml of hEGF qid for 32 days appeared to produce faster initial healing of the wound compared with control, although the wound recurred in both hEGF and control groups. These results suggest that hEGF may be helpful in some epithelial disorders in humans, although considerations of dose response and optimal dosing regimens must be addressed.Keywords:
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Human recombinant epidermal growth factor (hEGF) was evaluated in various corneal wound healing models in the rabbit. Human EGF accelerated epithelial wound healing in corneal reepithelialization, anterior-keratectomy, and alkali-burn models at concentrations of 10-500 micrograms/ml given four times daily (qid). In the corneal reepithelialization model, 100 micrograms/ml of hEGF qid produced a 45% increase in the wound-healing rate compared with control (0.13 versus 0.09 mm/hr) with a similar response at 500 micrograms/ml qid. In the anterior-keratectomy model, 500 micrograms/ml of hEGF qid accelerated healing by 40% (0.07 versus 0.05 mm/hr), although the 100 micrograms/ml dose was not active in this model, and 1 microgram/ml of hEGF actually slowed the healing rate. In the alkali-burn model, 10 and 100 micrograms/ml of hEGF qid for 32 days appeared to produce faster initial healing of the wound compared with control, although the wound recurred in both hEGF and control groups. These results suggest that hEGF may be helpful in some epithelial disorders in humans, although considerations of dose response and optimal dosing regimens must be addressed.
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We investigated the effect of epidermal growth factor (EGF) on rabbit corneal endothelial wound healing in vivo. After a 6 mm-diameter metallic cryoprobe was applied to rabbit corneas, 0.1 ml of recombinant human EGF (100 micrograms/ml) or saline was injected into the anterior chamber. Corneas were excised on 1, 2, and 7 days postoperatively, labeled with 3H-thymidine and subjected to autoradiography. Some corneas were examined by scanning electron microscopy. Autoradiography showed that the number of endothelial cells incorporating 3H-thymidine in corneas treated with EGF was significantly greater than that in the control. Scanning electron microscopy demonstrated the effect of EGF on accelerating endothelial healing. These findings indicate that EGF has a stimulatory effect on the proliferation of wounded rabbit corneal endothelial cells in vivo. Under the conditions tested in the present study, there were no side effects of EGF such as neovascularization or cellular proliferation in the angle. The results suggest that EGF might be clinically applicable for corneal endothelial disorders.
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We investigated the effect of epidermal growth factor (EGF) on keratocytes during corneal wound healing focusing on cell proliferation. A penetrating linear incision was made in the center of rabbit corneas. The corneas were then treated with eye drops of recombinant human EGF (10 micrograms/ml) or physiological saline (control) four times a day. After 1, 2, 3, and 7 days, the corneas were excised, labeled with 3H-thymidine (10 microCi/ml) at 37 degrees C for 4 hours and subjected to autoradiography. The results demonstrated increased number of keratocytes incorporating 3H-thymidine on the 1st, 2nd, 3rd and 7th days of healing and accelerated stromal wound healing in corneas treated with EGF compared with the controls. Thus, EGF stimulates of proliferation keratocyte and promotes corneal stromal wound healing.
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The role of salivary epidermal growth factor (EGF) in wound healing of the tongue was studied in mice. Sialoadenectomy (removal of the submandibular glands, which are the major source of salivary EGF) or sham operation was performed 2 wk before infliction of wound on the tongue. Salivary EGF levels were 1.98 +/- 0.47 and 0.20 +/- 0.04 (SE) microgram/ml in sham-operated male and female mice, respectively, whereas sialoadenectomy reduced salivary EGF to undetectable levels in both male and female mice. A circular superficial wound measuring approximately 2 mm in diameter was made in the middle of the tongue by mechanically ablating only the epithelial layer. The rate of wound healing was monitored by a stereomicroscopy. Sialoadenectomized male mice showed a significant delay in wound healing compared with sham-operated controls. Treatment of sialoadenectomized male mice with EGF (1 microgram/ml in drinking water) restored the rate of wound healing to normal levels. Transforming growth factor (1 microgram/ml) was as effective as EGF in the promotion of wound healing, whereas nerve growth factor (1 microgram/ml) was ineffective. Essentially the same results were obtained in female mice. In addition, two classes of EGF binding sites with high and low affinity were demonstrated in the epithelium of the tongue obtained from male and female mice. The maximum binding sites and dissociation constants of the EGF receptors were the same between males and females and were not affected by sialoadenectomy. These results suggest that salivary EGF is involved in the promotion of wound healing of the tongue in both male and female mice.
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To investigate the effects of recombinant epidermal growth factor on the wounded corneal healing after excision of pterygium.Simple and unrecurrent pterygium was selected, excised and sewed up conjunctival flap under local anaesthesia and microscope. After operation two drops of EGF eyedrop were used, and five minutes later 0.3% Tarivid Eye Oint was used again, and then the operated eye was enswathed. Everyday the wound cornea was observed and the EGF eyedrop was used.The wound cornea healing time of control group was seven days and that of the EGF group was five days and gave a remarkable difference (P < 0.05). The same results were obtained after comparing the effective group and ineffective group, P < 0.05.EGF eyedrop can accelerate proliferation and recovery of wound corneal epithelial cells. In the clinical trial, every body felt well and no side-effect was observed.
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The dose-dependent effect of epidermal growth factor (EGF) on the development of wound tensile strength following full-thickness corneal wounds was evaluated in 60 adult rabbits. One eye from each rabbit received a single 7-mm long corneal incision. After injury each rabbit was treated three times daily for 5 or 10 days with either EGF at 0.001 mg/ml (10 eyes), 0.01 mg/ml (10 eyes), 0.1 mg/ml (10 eyes), 1.0 mg/ml (15 eyes), or vehicle (15 eyes). The tensile strength of the wound was evaluated using a 5-mm wide strip of cornea mounted on a tensiometer. We found that EGF at 0.1 mg/ml and at 0.01 mg/ml increased wound strength by 100% at 5 days and by 60% at 10 days (P less than 0.05 and P less than 0.05). However, EGF at 0.001 mg/ml and 1.0 mg/ml appeared to have no effect on wound strength. Histologic examination of full-thickness wounds in a separate series showed an increase in wound fibroblastic response and a diminished fibrin clot at 5 days in rabbits treated with 0.1 mg/ml and 0.01 mg/ml. We conclude that EGF enhances the wound strength of full-thickness corneal wounds in a dose-dependent manner which may be explained in part by an increased fibroblastic response. Concentrations of EGF greater or less than an optimal dose may be less effective in enhancing corneal wound strength.
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