Stromal interleukin-1 expression in the cornea after haze-associated injury

Abstract

The purpose of this study was to determine whether myofibroblasts or other cells in the stroma in the cornea produce interleukin (IL)-1α or IL-1β that could modulate myofibroblast viability in corneas with haze after photorefractive keratectomy (PRK). Twenty-four female rabbits had haze-generating PRK for 9 diopters of myopia and were sacrificed at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims were removed, frozen in OCT at −80 °C, and analyzed by immunocytochemistry using primary antibodies to IL-1α, IL-1β and alpha smooth muscle actin (SMA). Double immunostaining was performed for the co-localization of SMA with IL-1α or IL-1β. Central dense haze and peripheral slight haze regions of each cornea were analyzed. SMA+ cells that expressed IL-1α protein were detected in both regions of the corneas at most time points following PRK. However, in the haze region at the 1, 3 and 4 week time points, significantly more ( p < 0.01) SMA+ cells did not express IL-1α. Also, in the haze region at all three time points, significantly more ( p < 0.01) SMA- cells than SMA+ cells expressed interleukin-1α protein. IL-1β expression patterns in SMA+ and SMA- stromal cells was similar to that of IL-1α after PRK. Previous studies have demonstrated that IL-1α or IL-1β triggers myofibroblast apoptosis in vitro, depending on the available concentration of apoptosis-suppressive TGFβ. This study demonstrates that SMA- cells such as corneal fibroblasts, keratocytes, or inflammatory cells may produce IL-1α and/or IL-1β that could act in paracrine fashion to regulate myofibroblast apoptosis—especially in the region where there is haze in the cornea after PRK was performed and SMA+ myofibroblasts are present at higher density. However, some SMA+ myofibroblasts themselves produce IL-1α and/or IL-1β, suggesting that myofibroblast viability could also be regulated via autocrine mechanisms.