title: Interleukin-1 receptor role in the viability of corneal myofibroblasts.
abstract: The purpose of this study was to investigate the role of interleukin-1 (IL-1) in modulating myofibroblast viability in mouse corneas with stromal opacity. Twenty-four female B6; 129S1-Il1r1tm1Roml/J homozygous IL-1RI knockout mice and 24 control B6129SF2/J mice were included in this study. Each mouse had opacity-generating irregular phototherapeutic keratectomy (PTK) performed with an excimer laser in one eye. Groups of 8 mice from each group were euthanized at one month, three months and six months after surgery and the eyes cryo-preserved. The contralateral eye served as unwounded control. Immunohistochemistry was performed for α-smooth muscle actin (SMA) in central sections of all corneas. The TUNEL assay for apoptosis was performed on 8 sections of four eyes from each group. No SMA+ cells were detected in the stroma of unwounded control or knockout corneas. SMA+ myofibroblast density was significantly higher (p < 0.001) in the IL-1RI knockout group than in the control group at one month, three and six months after irregular PTK. Mean TUNEL+ stromal cells in the anterior 50 μm of stroma was significantly lower in the IL-1RI knockout group compared to the control group at six months after irregular PTK (p = 0.04). These results corroborate the findings of recent in vitro work that demonstrated an antagonistic effect of TGFβ and IL-1 on myofibroblast viability, and found that IL-1-triggered myofibroblast apoptosis was suppressed by TGFβ. Thus, IL-1 is an important modulator of myofibroblast viability during corneal wound healing.
authors.affiliation: The Cole Eye Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave. Cleveland, OH 44195, United States.
authors.forename: F L
authors.initials: FL
authors.lastname: Barbosa
authors.forename: M
authors.initials: M
authors.lastname: Lin
authors.forename: M R
authors.initials: MR
authors.lastname: Santhiago
authors.forename: V
authors.initials: V
authors.lastname: Singh
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; D002470:Cell Survival; D003318:Corneal Opacity / Q000473:pathology*; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology*; D018903:Photorefractive Keratectomy; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D014945:Wound Healing
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D017472:Receptors, Interleukin-1