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Y.-T. Chen, S. Lazarev, M. Gallup, N. McNamara; Interleukin-1 is a Determinant for Ocular Mucin Alteration in Autoimmune Regulator-Mediated Keratinizing Squamous Metaplasia. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1561.
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© ARVO (1962-2015); The Authors (2016-present)
Sjögren syndrome (SS) causes an autoimmune-mediated keratoconjunctivitis sicca (KCS) that leads to ocular squamous metaplasia (SM), a keratinizing disease of ocular surface coupled with abnormal mucin alteration. Although the proinflammatory cytokine IL-1 has been implicated in the pathogenesis of SS-KCS, its contribution to the pathological mucin profile and cell surface glycoconjugate change in keratinizing SM of ocular surface remains unclear. Using mice deficient in autoimmune regulator gene (Aire) as a SS animal model, we investigated the mucin changes in SM disease in the presence and in the absence of IL-1 receptor signaling.
Aire-/- single knock out (SKO) and Aire-/- IL-1R-/- double knockout (DKO) mice with wild-type (WT) controls were used to evaluate the role of IL-1 in Aire-mediated SM. Epithelial integrity was scored by lissamine green (LG) staining. Keratinization was quantified by the expression of small proline-rich protein 1B (SPRR1b) in the cornea. Mucin profile was studied with anti-MUC5AC Ab, anti-MUC1 Ab. Glycoconjugates of goblet cell mucin and ocular epithelia were determined by Acian blue-Periodic acid Schiff (AB-PAS) staining and lectin Maakia amurensis agglutinin (MAA), respectively. Staining intensity was quantified by NIS Elements and expressed in arbitrary units.
LG staining intensity,104.2+32.5 in SKO, was significant higher than 15.3+21.3 in WT and 52.12 + 20.3 in DKO (p < .01). SPRR1b,105.3 + 21.7 in SKO, was higher than 47.4 + 19.0 in WT and 63.1 + 17.7 in DKO (p < .05). Compared to WT and DKO, MUC1 decreased in limbus in SKO, whereas MUC5AC revealved no difference among 3 groups. AB+ goblet cells in total AB/PAS stained cell showed 55.0 + 36.5 % in SKO, versus 2.9 + 3.47 in WT and 19.8 + 13.1 (p < .01). In comparison to WT and DKO, MAA lectin study revealed an upregulated expression of α-2,3 bond sialylated glycoconjugates in corneal epithelium of SKO. Regression analysis showed both LG and AB/PAS staining are good predictors of SPRR1b expression (R2=0.48 and 0.56, respectively, p< .02).
Characteristics of SM include damaged corneal epithelium, corneal keratinization, GC mucin acidification and increased sialylated glycoconjugates. IL-1R signaling attenuates SM disease by reducing ectopic expression of keratinizing protein SPRR1b, preventing MUC1 mucin decrease in limbal epithelium, inhibiting GC mucin acidification, and reducing corneal sialylated glycoconjugates in SM. Data suggest an integral role of IL-1R signaling in mediating multiple Aire-mediated SM events.
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