title: 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)-1alpha or IL-1beta 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 degrees C, and analyzed by immunocytochemistry using primary antibodies to IL-1alpha, IL-1beta and alpha smooth muscle actin (SMA). Double immunostaining was performed for the co-localization of SMA with IL-1alpha or IL-1beta. Central dense haze and peripheral slight haze regions of each cornea were analyzed. SMA+ cells that expressed IL-1alpha 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-1alpha. Also, in the haze region at all three time points, significantly more (p<0.01) SMA- cells than SMA+ cells expressed interleukin-1alpha protein. IL-1beta expression patterns in SMA+ and SMA- stromal cells was similar to that of IL-1alpha after PRK. Previous studies have demonstrated that IL-1alpha or IL-1beta triggers myofibroblast apoptosis in vitro, depending on the available concentration of apoptosis-suppressive TGFbeta. This study demonstrates that SMA- cells such as corneal fibroblasts, keratocytes, or inflammatory cells may produce IL-1alpha and/or IL-1beta 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-1alpha and/or IL-1beta, suggesting that myofibroblast viability could also be regulated via autocrine mechanisms.
authors.affiliation: Cole Eye Institute, The Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA.
authors.forename: F L
authors.initials: FL
authors.lastname: Barbosa
authors.forename: S S
authors.initials: SS
authors.lastname: Chaurasia
authors.forename: H
authors.initials: H
authors.lastname: Kaur
authors.forename: F W
authors.initials: FW
authors.lastname: de Medeiros
authors.forename: V
authors.initials: V
authors.lastname: Agrawal
authors.forename: S E
authors.initials: SE
authors.lastname: Wilson
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D003318:Corneal Opacity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D053582:Interleukin-1alpha / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D009216:Myopia / Q000601:surgery; D018903:Photorefractive Keratectomy; D011183:Postoperative Complications; D011817:Rabbits
chemical_list: D000199:Actins; D053582:Interleukin-1alpha; D053583:Interleukin-1beta