Abstract
Purpose:
Following an injury leading to the loss of the corneal epithelium, the remaining epithelial cells immediately attempt to close the defect. Poor healing of epithelial wounds is a major clinical problem, leading to persistent epithelial defects and ulceration. We previously showed that carbohydrate-binding protein galectin-3 (Gal-3) enhanced wound closure in explanted monkey corneas lacerated by n-heptanol. Alkali injuries of the eye often cause extensive damage to the cornea due to rapid penetration and damage to deeper ocular structures. The purpose of the present experiment was to study Gal-3 in the more severe alkali burn model, and to compare results to the n-heptanol model.
Methods:
An alkali burn was created by a 60 sec application of a 7.5 mm diameter filter disc soaked in 1N sodium hydroxide onto the central cornea of enucleated monkey eyes. The corneas were then excised, incubated for various times with or without recombinant Gal-3, and stained with 1% sodium fluorescein. Corneal wound closure was quantified by digital image analysis.
Results:
After an alkali burn, the corneal wound area became smaller in a time-dependent manner. Exogenous recombinant Gal-3 enhanced this wound closure to the same extent as in corneas wounded with n-heptanol. However, data suggested that the rates of healing were different in the two models.
Conclusions:
Exogenous Gal-3 showed a beneficial effect on closure of wounds caused by either alkali or n-heptanol. In both cases, this may be because Gal-3 binds to ECMs such as laminin and collagen and promotes lamellipodia formation by cross-linking to α3 integrin. Although initial cytokines released from local cells may be different in our two chemical models, the results indicate that Gal-3 may be a candidate drug to enhance epithelialization in human cornea damaged by variable causes. Dr. Shearer receives a research contract and consulting fees from, and Dr. Azuma and Ms. Fujii are employees of, Senju Pharmaceutical Co. Ltd.
Keywords: 765 wound healing •
482 cornea: epithelium