Abstract
Purpose: :
IL-1 has been shown to be an important cytokine involved in regulating wound healing and inflammation in the injured cornea. The present study investigated the effect of topical application of IL-1 receptor antagonist (IL-1Ra) in blocking the entry of inflammatory cells into the scrapped cornea and corneal myofibroblast generation after PRK in rabbit corneas.
Methods: :
Two different experiments were performed. In the preliminary phase designed to verify the IL-1 receptor antagonist functioned in rabbits, five rabbits were divided into two groups of control BSS (2 rabbits) and IL-1Ra (Amgen) (3 rabbits) treatments. One cornea from each rabbit was scraped and IL-1Ra at the dose of 20 mg/ml or BSS was applied topically every 6 hours for 24 hours. Rabbits were sacrificed after 24 hr and corneal rims were preserved in OCT. 8-10 micron sections were cut and stained with Cd11b, a marker for monocytes. In the second phase to test the effect of the IL-1Ra on myofibroblast generation and haze, twelve rabbits were divided into two groups of 6 rabbits each and treated with control BSS or IL-1Ra, respectively. -9.0 diopter PRK on left eye was performed in each animal and the IL-1Ra at 20 mg/ml or BSS was applied topically every 6 hours for 24 hours in the respective groups. Rabbits were sacrificed after 1 month. Corneal rims were preserved in OCT, sections were cut and immunohistochemistry for a-smooth muscle actin (SMA) was performed.
Results: :
Cd11b+ cells counted at 400X field were significantly higher in the BSS group indicating the presence of increased inflammation compared to the IL-1Ra treated group in scrapped rabbit corneas (79.4+0.1 in the BSS treated group and 15.2+0.9 in the IL-1Ra treated group, p<0.001). This result indicated that the IL-1Ra functioned to block IL-1 effects in rabbits. In the PRK treated corneas collected after one month, IL-1Ra treatment significantly reduced the myofibroblast generation (44.2+2.9 SMA+ cells/400X field in the BSS group and 20.3+1.9 SMA+ cells/400X field in the IL-1Ra treated group, p<0.001). However, haze monitored at the slit lamp at one month after surgery was not significantly different between IL-1Ra and control group.
Conclusions: :
IL-1Ra antagonist decreased SMA+ myofibroblasts in the stroma at one month after 9-diopter PRK. The mechanism of this decrease is unknown. Possibilities include interference with the recruitment of non-resident progenitor cells to myofibroblasts or interference with the development of myofibroblasts. Interestingly, there was no difference in corneal opacification (haze) between the two groups at one month.
Keywords: wound healing • cornea: stroma and keratocytes • cytokines/chemokines