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1557-77322532009JunJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and TherapeuticsJ Ocul Pharmacol TherLong-term topical cyclosporine treatment improves tear production and reduces keratoconjunctivitis in rabbits with induced autoimmune dacryoadenitis.285292285-9210.1089/jop.2008.0138To use a rabbit model of induced autoimmune dacryoadenitis to evaluate the efficacy of topical ophthalmic cyclosporine A (CsA).Autoimmune dacryoadenitis was induced by injecting autologous peripheral blood lymphocytes, which had been activated in a mixed cell reaction with acinar cells isolated from one inferior lacrimal gland (LG), back into the donor animal's remaining inferior LG. Schirmer's test, tear breakup time, and rose Bengal staining were assessed. Animals with established disease were treated topically with either CsA or Endura twice daily for 5 months.Without treatment tear production and tear stability were abnormal for 6 months, and clear signs of ocular surface defects were evident. Severe immune cell infiltration was observed in the LG. Long-term CsA treatment increased tear production only slightly, but the severity of LG histopathology decreased noticeably. CD4(+) T-cell infiltration of the LG was decreased and infiltration by MHC class II-expressing cells was also decreased. For the Endura-treated group tear production did not improve, rose Bengal scores remained high, and histopathology showed infiltration comparable to the untreated group, but by the end of the study the tear breakup time did improve.The rabbit model of autoimmune dacryoadenitis had signs of chronic dry eye disease 6 months after induction of disease. Tear production improved slightly with CsA treatment and CD4(+) T-cell infiltration decreased significantly in the LG. This suggests that some Sjögren's patients may benefit from long-term CsA treatment.ThomasPadmaja BPBOcular Surface Center, Department of Ophthalmology, Doheny Eye Institute, Los Angeles, CA 90033, USA.SamantDeedar MDMZhuZejinZSelvamShivaramSStevensonDouglasDWangYanruYSongSang WSWMircheffAustin KAKSchechterJoel EJEYiuSamuel CSCTrousdaleMelvin DMDengR01 EY012689-01A1EYNEI NIH HHSUnited StatesJournal Article
United StatesJ Ocul Pharmacol Ther95110911080-76830Immunosuppressive Agents83HN0GTJ6DCyclosporineIMAdministration, TopicalAnimalsAutoimmune DiseasescomplicationsimmunologypathologyCyclosporineadministration & dosageimmunologytherapeutic useDacryocystitiscomplicationsimmunologypathologyDrug Administration ScheduleDry Eye SyndromesetiologyimmunologypathologyFemaleImmunosuppressive Agentsadministration & dosageimmunologytherapeutic useKeratoconjunctivitiscomplicationsdrug therapyphysiopathologyRabbitsT-LymphocytesimmunologypathologyTearsmetabolism200952290200952290200981190201061ppublish19456259NIHMS180017PMC283861110.1089/jop.2008.0138Fox R.I. Kang H.I. Pathogenesis of Sjogren's syndrome. Rheum. Dis. Clin. North Am. 1992;18:517–538.1323135Lemp M.A. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J. 1995;21:221–232.8565190Sullivan D.A. Edwards J.A. Androgen stimulation of lacrimal gland function in mouse models of Sjogren's syndrome. J. Steroid Biochem. Mol. Biol. 1997;60:237–245.9191982Stevenson D. Tauber J. Reis B.L. Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. The Cyclosporin A Phase 2 Study Group. Ophthalmology. 2000;107:967–974.10811092Sall K. Stevenson O.D. Mundorf T.K., et al. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000;107:631–639.10768324Barabino S. Dana M.R. Dry eye syndromes. Chem. Immunol. Allergy. 2007;92:176–184.17264493Zhu Z. Stevenson D. Schechter J.E., et al. Lacrimal histopathology and ocular surface disease in a rabbit model of autoimmune dacryoadenitis. Cornea. 2003;22:25–32.12502944Niederkorn J.Y. Stern M.E. Pflugfelder S.C., et al. Desiccating stress induces T cell-mediated Sjogren's Syndrome-like lacrimal keratoconjunctivitis. J. Immunol. 2006;176:3950–3957.16547229Pflugfelder S.C. Tseng S.C. Sanabria O., et al. Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation. Cornea. 1998;17:38–56.9436879Pflugfelder S.C. Solomon A. Dursun D., et al. Dry eye and delayed tear clearance: “a call to arms.”. Adv. Exp. Med. Biol. 2002;506:739–743.12613986Kaswan R.L. Martin C.L. Chapman W.L., Jr. Keratoconjunctivitis sicca: histopathologic study of nictitating membrane and lacrimal glands from 28 dogs. Am. J. Vet. Res. 1984;45:112–118.6703444Kaswan R.L. Martin C.L. Dawe D.L. Rheumatoid factor determination in 50 dogs with keratoconjunctivitis sicca. J. Am. Vet. Med. Assoc. 1983;183:1073–1075.6643212Kaswan R.L. Martin C.L. Dawe D.L. Keratoconjunctivitis sicca: immunological evaluation of 62 canine cases. Am. J. Vet. Res. 1985;46:376–383.3888007Pflugfelder S.C. Anti-inflammatory therapy of dry eye. Ocul. Surf. 2003;1:31–36.17075627Baudouin C. Liang H. Amplifying factors in ocular surface diseases: apoptosis. Ocul. Surf. 2005;3:S194–S197.17216118Kaswan R.L. Salisbury M.A. Ward D.A. Spontaneous canine keratoconjunctivitis sicca. A useful model for human keratoconjunctivitis sicca: treatment with cyclosporine eye drops. Arch. Ophthalmol. 1989;107:1210–1216.2757551Kunert K.S. Tisdale A.S. Gipson I.K. Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine. Arch. Ophthalmol. 2002;120:330–337.11879137Pflugfelder S.C. De Paiva C.S. Villarreal A.L., et al. Effects of sequential artificial tear and cyclosporine emulsion therapy on conjunctival goblet cell density and transforming growth factor-beta2 production. Cornea. 2008;27:64–69.18245969Pflugfelder S.C. Antiinflammatory therapy for dry eye. Am. J. Ophthalmol. 2004;137:337–342.14962426Guo Z. Song D. Azzarolo A.M., et al. Autologous lacrimal-lymphoid mixed-cell reactions induce dacryoadenitis in rabbits. Exp. Eye Res. 2000;71:23–31.10880273Zhu Z. Stevenson D. Ritter T., et al. Expression of IL-10 and TNF-inhibitor genes in lacrimal gland epithelial cells suppresses their ability to activate lymphocytes. Cornea. 2002;21:210–214.11862098Trousdale M.D. Zhu Z. Stevenson D., et al. Expression of TNF inhibitor gene in the lacrimal gland promotes recovery of tear production and tear stability and reduced immunopathology in rabbits with induced autoimmune dacryoadenitis. J. Autoimmune Dis. 2005;2:6.PMC118791515985164Lemp M.A. Management of dry eye disease. Am. J. Manag. Care. 2008;14:S88–S101.18452372Hyon J.Y. Lee Y.J. Yun P.Y. Management of ocular surface inflammation in Sjogren's syndrome. Cornea. 2007;26:S13–S15.17881909Thomas P.B. Zhu Z. Selvam S., et al. Autoimmune dacryoadenitis and keratoconjunctivitis induced in rabbits by subcutaneous injection of autologous lymphocytes activated ex vivo against lacrimal antigens. J. Autoimmun. 2008;31:116–122.PMC261063018534818Duncan N. Craddock C. Optimizing the use of cyclosporin in allogeneic stem cell transplantation. Bone Marrow Transplant. 2006;38:169–174.16751787Wang Y. Ogawa Y. Dogru M., et al. Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease. Bone Marrow Transplant. 2008;41:293–302.17982500Lelli G.J., Jr. Musch D.C. Gupta A., et al. Ophthalmic cyclosporine use in ocular GVHD. Cornea. 2006;25:635–638.17077652Pepose J.S. Akata R.F. Pflugfelder S.C., et al. Mononuclear cell phenotypes and immunoglobulin gene rearrangements in lacrimal gland biopsies from patients with Sjogren's syndrome. Ophthalmology. 1990;97:1599–1605.1965021Oak J.S. Deane J.A. Kharas M.G., et al. Sjogren's syndrome-like disease in mice with T cells lacking class 1A phosphoinositide-3-kinase. Proc. Natl. Acad. Sci. USA. 2006;103:16882–16887.PMC163654817071741