Abstract
Purpose:
To develop a delayed wound healing model for evaluating corneal wound healing capabilities for persistent corneal epithelial defects (PCED) as in the cases of chronic ocular infections, severe dry eye, neurotrophic/diabetic keratitis, chemical and exposure to blast traumas as in a military theater. Most preclinical epithelial defect models heal very rapidly thus the impact on wound healing is difficult to determine.
Methods:
Animals were anesthetized with ketamine and xylazine given intramuscularly (IM). The epithelial defect was created in the center of the cornea with an 8.5 mm Camellin LASEK alcohol well. A 20% ethyl alcohol solution was applied for 2.5 minutes. The ocular surface outside the Camellin well was irrigated with balance salt solution (BSS) during alcohol application. The alcohol solution was removed and cornea was irrigated with BSS. The epithelium was removed (to the stromal region of the cornea) by scraping with Bard-Parker blade #15. Buprenorphine was given as postoperative analgesia. In order to evaluate the healing mechanism of a PCED condition, and since steroids have ability to delay healing, all groups were dosed with Dexmaethasone (DEX). Recombinant human growth hormone (rHGH) was chosen as a positive control; rHGH has been shown to accelerate wound healing. BSS served as a negative control. All animals started treatment on Day 1 post surgery. Each test group was dosed topically with DEX (50µL) QID within 8 hrs. The rHGH-DEX (n=5) and BSS-DEX (n=4) were dosed topically QID (50µL) at least 30 min. after the DEX treatment. One group consisted of DEX treatment only (n=4). Clinical ophthalmic examinations, including slit lamp biomicroscopy and fluorescein staining, were performed twice daily on days 2, 3, 4, and once on day 5. Percentage of corneal wound healing was evaluated and compared across treatment groups. The groups were compared statistically and histopathologically.
Results:
Day 2 through day 5, the DEX group was inhibited in corneal wound healing rate. DEX-BSS and DEX-rHGH were similar on day 2. By day 3 to day 4 the DEX-rHGH was significantly faster in corneal wound healing rate when compared to the DEX-BSS. By day 4 PM and day 5 both DEX-rHGH and DEX-BSS were similar.
Conclusions:
This model can offer the opportunity for evaluating pharmacological agents and drug delivery systems that can promote corneal wound healing for PCED conditions.
Keywords: 765 wound healing •
482 cornea: epithelium •
480 cornea: basic science