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S. B. Pangelinan, C. S. De Paiva, R. Singh, K. Agusala, W. J. Farley, M. Stern, S. C. Pflugfelder; Topical Cyclosporine Emulsion Modulates Immune Response in Experimental Dry Eye. Invest. Ophthalmol. Vis. Sci. 2008;49(13):440.
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To investigate the effect of topical Cyclosporine (CsA) 0.05% treatment on the local immune response to experimental murine dry eye.
Experimental dry eye (EDE) was induced in 3 groups of C57BL6 mice by cholinergic blockade and exposure to a desiccating environment for 5 days. The dry eye control group received no topical therapy, a second group received 1uL of 0.05% cyclosporine ophthalmic emulsion QID (EDE + CsA) and a third group received 1uL of CsA vehicle (polysorbate 80 1%, glycerin 1%) QID. Eyes and ocular adnexa were excised, cryosectioned, and evaluated for goblet cell density, CD4+ and CD8+ T cell infiltration and TGFβ and CD103 expression. Goblet cells were counted in periodic acid Shiff (PAS)-stained sections. Antigens were detected by immunohistochemistry and immunofluorescent confocal microscopy.
Dry eye induced migration of CD4+ T cells into the goblet cell rich area of the conjunctival epithelium, the density of CD8+ T cells; CD103 and TGFβ2 staining decreased in the same area. Treatment with topical CsA reduced CD4+ T cell migration and promoted a significant increase in CD8+ T cells in comparison to the EDE 5D control group. Goblet cell density was maintained in the CsA group. A significant direct correlation was noted between the density of CD8+ T cells and goblet cells (p<0.001). The CsA treated group had a significantly greater number of CD103+ cells and greater TGFβ2 expression than the EDE 5D or the vehicle groups.
Topical CsA significantly reduces conjunctival CD4+ T cell infiltration, and promotes intraepithelial CD8+ T cell migration protecting against the goblet cell loss in experimental murine dry eye.
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