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A. Solomon, Y. Ivanir, F. Orucov, J. Pe'er, J. Frucht–Pery; Increased Expression of Inflammatory Cytokines and Cathepsins in the Corneal Epithelium in Keratoconus . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4380.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the expression of inflammatory cytokines and cathepsins in the corneal epithelium in keratoconus.
Tissue sections were prepared from paraffin fixed blocks of corneal buttons removed during penetrating keratoplasty from 29 patients who had keratoconus. Tissue sections from 10 age–matched eyes enucleated because of uveal melanoma served as a control. Expression of Interleukin (IL)–1, IL–6, tumor necrosis factor (TNF)–α, and cathepsins (Cath) B, S, L and D in the corneal epithelium was evaluated by immuno– histochemistry. Digital image analysis using ImagePro–Plus software (Media Cybernetics, Silver Springs, MD) was performed to quantify the expression of the various cytokines and cathepsins. A mean intensity stain index (ISI), based on the staining density and the area stained, was calculated from digital images captured from sequential areas of the corneal epithelium. The mean ISI of sections from patients with keratoconus was compared to that of controls for each cytokine and cathepsin tested, using the Mann–Whitney’s test. Clinical parameters were retrospectively recorded from the corresponding patients’ charts including the age at diagnosis, years with keratoconus prior to surgery, age at surgery, and maximal central topographic K reading. The correlation between the clinical parameters and the ISI values for each protein was evaluated by factor analysis and Spearman’s rank correlation.
A significantly higher mean protein expression in the corneal epithelium of keratoconus corneas was demonstrated for IL–1ß (ISI score in keratoconus 43,086 ± 32,829 compared to 9,354 ± 15,214 in normal controls, p=0.00017), IL–6 (31.63 ± 22.4 in keratoconus vs. 10.76 ± 21.41 in controls, p=0.024), TNFα (3,402,263 ± 1,516,245 in keratoconus vs. 1,933,844 ± 1,467,971 in controls, p=0.021) and Cath B (11.08 ± 10.30 in keratoconus vs. 3.51 ± 5.87 in controls, p=0.011). Higher though not significant expression was also demonstrated for Cath D, Cath L and Cath S, who had 1.3, 2.1, and 1.9 folds higher ISI values compared to controls, respectively. A highly significant correlation was found between the patients age at diagnosis of keratoconus and the ISI values of IL–1ß (r=0.8047, p=0.0072) and TNFα (r=0.8047, p=0.0039).
The corneal epithelium in keratoconus expresses high levels of cytokines and enzymes, which are associated with inflammation and tissue degradation. As the expression of these mediators increase with the patients’ age, these data may partially explain the continuous progression in corneal thinning which is typical in keratocnus.
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