Abstract
Purpose: :
To analyze interleukin (IL) -1α and IL-1β production in smooth muscle actin (SMA) + myofibroblasts and SMA- cells in rabbit corneas with stromal haze that had -9 diopter photorefractive keratectomy (PRK) and unwounded control corneas.
Methods: :
Rabbits that had -9 diopter PRK in one eye were euthanized at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery and the corneo-scleral rims cryo-preserved in OCT. The contralateral eyes served as unwounded control eyes. There were six PRK corneas at each time point. Seven µm thick sections were cut with a keratome. Double- immunohistochemistry was performed for SMA and IL-1α or IL-1β in the unwounded and wounded corneas.
Results: :
No SMA+ cells and only rare IL-1α+ or IL-1β+ stromal cells were detected in unwounded corneas. At 1, 2, 3, and 4 weeks after PRK, both SMA+ myofibroblasts and SMA- stromal cells expressed IL-1α and IL-1β. However, statistically significantly (p<0.05) more SMA- cells than SMA+ cells expressed both IL-1α and IL-1β at each time point after surgery. IL-1α appeared to be expressed at higher levels than IL-1β in stromal cells, based on the intensity of staining.
Conclusions: :
Recent in vitro studies in mouse myofibroblast cells have demonstrated an antagonistic effect of TGFβ and IL-1 on myofibroblast viability. TGFβ, likely from the corneal epithelium in the context of epithelial basement membrane structural and/or functional defects, promotes development and maintains viability of myofibroblasts. IL-1 promotes myofibroblast apoptosis, but this effect is suppressed by TGFβ. Once stromal TGFβ levels fall, IL-1 triggers myofibroblast apoptosis. This study suggests that both SMA+ myofibroblasts themselves and other SMA- stromal cells are potential sources of IL-1 (both IL-1α and IL-1β) that triggers myofibroblast apoptosis, although SMA- cells are predominant producers of both IL-1α and IL-1β after haze-producing injury. Thus, myofibroblast apoptosis could be triggered by either paracrine or autocrine IL-1 (autocrine suicide) when TGFβ levels in the stroma fall.
Keywords: cytokines/chemokines • cornea: stroma and keratocytes • cornea: basic science