Abnormalities in corneal wound healing are a major health care problem. There are a number of clinical conditions where corneal wound healing is compromised, for example, herpes simplex keratitos, diabetes mellitus, and rheumatoid disease. Cornea healing is also an important complicating factor in various surgical procedures involving the cornea and cateracts. Excessive epithelial migration through a corneal or limbal wound can epithelialize the anterior chamber of the eye and cause secondary glaucoma. Evidence from refractive surgery suggests that corneal scarring can be unpredictable and incomplete. This proposal will examine the ability of fibronectin fragments and chemically synthesized peptides to promote in vitro and in vivo corneal epithelial wound healing in model systems. Fibronectin is a multidomain molecule which is involved in the normal wound healing in the eye. Exogenous FN will promote healing of chronic corneal ulcers. We will isolate specific proteolytic fragments added to an in vitro model to determine whether the rate of healing is increased. The next studies will determine the effects of these fragments or peptides in promoting isolated epithelial cell movement in vitro. To aid in vivo studies, we will next use radiolabelled FN peptides or fragments and determine binding to corneas in vitro in 3 vehicles which may increase peptide exposure in the cornea: polyvinyl alcohol, petrolatum, and hyaluronic acid. The nexty studies will utilize bioactive peptides and fragments of fibronectin in vehicles in in vivo model systems of full and partial thickness wounds. Healing rate will be monitored by evaluating corneal healing serially in animals over 72 hours. Histological samples and morphometric analyses will be performed to confirm the in vivo results. The studies will hopefully provide an effective, safe (avoiding the risk of blood products) method using chemically synthesized peptides to deliver pharmaceuticals which will enhance corneal wound healing. This would also have application for diseases of the eye where there is abnormal wound healing. Modest success in this research program could have a major impact on serious health care problems.
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