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S. Song, P.B. Thomas, Z. Zhu, S. Selvam, D. Stevenson, A.K. Mircheff, J.E. Schechter, M.D. Trousdale; Prolonged Cyclosporin A Treatment Reduced the Severity of Experimental Autoimmune Dacryoadenitis in a Rabbit Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5580.
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To evaluate the effects of prolonged cyclosporin A treatment on lacrimal gland function, lacrimal histopathology, and ocular surface pathology in a rabbit model of experimental autoimmune dacryoadenitis.
An inferior lacrimal gland was excised from each rabbit, epithelial cells were purified and cultured for 2 days, gamma irradiated, and co–cultured for 5 days with autologous peripheral blood lymphocytes. The activated lymphocytes were injected into the remaining inferior lacrimal gland of the donor rabbit ("auto–adoptive transfer"). Clinical disease was evaluated by Schirmer test, tear break–up time and rose bengal staining. Rabbits with established disease were treated twice daily topically with either Cyclosporin A (Restasis) or vehicle (Endura) in a coded study. Signs were assessed every 2 weeks. After 6 months, the inferior and superior lacrimal glands were removed for analysis. The glands were sectioned and immunostained to quantify the CD4+ and CD8+ immune cell populations.
There was no significant difference in the clinical parameters during the 6–month period between the 2 groups; however, the histopathologic studies of inferior and superior lacrimal glands revealed a significant difference in the severity of the disease between the 2 groups. Lacrimal glands from rabbits treated with Endura had large amounts of perivascular and periductal lymphocytes. In contrast, lacrimal glands from rabbits treated with cyclosporin A appeared essentially normal and frequency of perivascular lymphocytes was similar to that of normal animals. There was a significant change in the CD4:CD8 ratio between the two groups.
Our rabbit model of autoimmune dacryoadenitis mimics Sjögren’s syndrome even 6 months after induction of disease in that tear production and tear break–up time remained abnormally low and corneal surface staining remained abnormally high. Cyclosporin A treatment appeared to have no beneficial effect on signs of ocular surface disease, but it greatly reduced the severity of lacrimal gland histopathology.
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