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S. Narayanan, R. M. Corrales, J. M. Herreras, V. Saez, Y. Cordero, M. Calonge; Cytokine Gene Expression in Conjunctival Epithelia of Dry Eye Patients. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4268.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have described expression of some inflammatory cytokines in human dry eye and other cytokines in experimental dry eye in mice. We investigated expression of several of these cytokines in the conjunctival epithelia of an older Caucasian dry eye population and compared them with healthy subjects.
Conjunctival impression cytology samples were obtained from 45 dry eye patients (16 male, 29 female; 62.7±8.3 years) (tear deficient with a Schirmer-1 score < 5mm wetting in 5 minutes) and 76 healthy subjects (36 male, 40 female; 62.6±8.3 years). Following RNA extraction and cDNA synthesis, real-time PCR was performed using Taqman probes to evaluate expression of the following genes studied previously: MMP-1, MMP-3, MMP-9, TRAIL, hBD-1 and hBD-2, as well as genes not studied before in dry eye: IFN-γ, TRAIL-R1, TRAIL-R2. The housekeeping gene (GAPDH) was amplified to normalize the amount of expression levels. No template controls and RNA were used to test contamination issues. Results were analyzed using the comparative Ct method. The results from healthy subjects were used as calibrator. The student t-test for independent samples was used to compare means between groups.
There was no difference in expression in conjunctival TRAIL, TRAIL-R1, TRAIL-R2, MMP-1, IFN-γ and hBD-1 between the two groups. Conjunctival MMP-3 (p<0.0001), MMP-9 (p<0.05) and hBD-2 (p<0.05) were significantly upregulated in the dry eye group.
The results from our study of an older Caucasian population support previous experimental as well as human data with respect to an inflammatory basis for dry eye disease. While previous studies have shown increased MMP-3 levels in tear fluid, ours is the first study to demonstrate that this stromelysin is increased in the conjunctival epithelia of dry eye patients. MMP-3 is an activator of MMP-9. Thus MMP-3 might play an important role in the pathogenesis of ocular surface damage in tear-deficient dry eye. Constitutive expression of TRAIL and its receptors may provide corneal protective benefits. hBD-2, which was also upregulated in dry eye patients in a previous smaller study, probably plays a defensive role at the ocular surface of dry eye patients who have a potential risk for microbial keratitis.
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