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S. S. Chaurasia, J. C. Ramos-Esteban, H. Kaur, V. Agrawal, S. E. Wilson; Effect of Topical IL-1 Receptor Antagonist in Reducing Alpha Smooth Muscle Actin+ Myofibroblast Generation After Photorefractive Keratectomy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3070.
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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.
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.
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.
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.
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