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P.L. Christopherson, G. Sosne; Thymosin ß4 Effects Corneal Cytokine, Chemokine and Extracellular Matrix Gene Expression Following Alkali Injury in the BALB/c Mouse . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1400.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:The purpose of this study was to determine the effect of thymosin ß4 (Tß4) treatment on the corneal inflammatory and tissue remodeling responses after alkali burn in BALB/c mice. Methods: Corneas from BALB/c mice were burned with a 2mm disc soaked in 1.0 N NaOH for 30 seconds. Eyes were irrigated copiously with PBS and then treated topically with either Tß4 (5 µg/5 µl PBS) or 5 µl PBS twice daily. At 1, 3 and 7 days, mice were sacrificed, the eyes enucleated and processed for histopathologic and mRNA analysis. Corneas from the Tß4- vs. PBS-treated groups (n=5/group/time point) were assayed for cytokine/chemokine and matrix (ECM) gene expression (96 murine genes/panel) using Superarray® (Rockville, MD) kits. Genes with an average of ≥ 2-fold change between the Tß4 and PBS groups were arbitrarily considered and were further tested by real time RT-PCR. Results: Overall, Tß4-treated mouse corneas demonstrated decreased inflammation and hyphema at 7 days after injury when compared to PBS-treated controls. Molecularly, Tß4-treated corneas exhibited decreased gene transcript mRNA levels for chemokine receptor 5, interleukin (IL)-11, IL-15 receptor alpha chain, thymus and activation regulated cytokine (TARC), macrophage inflammatory proteins (MIP)-1α and -2, Scyb15 (IL-8 homologue), stromal derived factor (SDF)-1α and -2. ECM gene transcript mRNA levels were decreased in the Tß4-treated mice for: cathepsin B, matrix metalloproteinase 14 (MT1-MMP), tissue inhibitor of metalloproteinase (TIMP)-1, serine protease inhibitor 7 (Maspin), tissue plasminogen activator (tPA), as well as ECM-1 and the thrombospondins (THBS)-1 and -2. Conclusions: The BALB/c mouse model of alkali injury appears useful for determining the molecular effects of Tß4 on corneal inflammation and ECM remodeling.
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