title: Long-term topical cyclosporine treatment improves tear production and reduces keratoconjunctivitis in rabbits with induced autoimmune dacryoadenitis.
abstract: OBJECTIVE
  To use a rabbit model of induced autoimmune dacryoadenitis to evaluate the efficacy of topical ophthalmic cyclosporine A (CsA).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Doheny Eye Institute, Los Angeles, CA 90033, USA.
authors.forename: Padmaja B
authors.initials: PB
authors.lastname: Thomas
authors.forename: Deedar M
authors.initials: DM
authors.lastname: Samant
authors.forename: Zejin
authors.initials: Z
authors.lastname: Zhu
authors.forename: Shivaram
authors.initials: S
authors.lastname: Selvam
authors.forename: Douglas
authors.initials: D
authors.lastname: Stevenson
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Sang W
authors.initials: SW
authors.lastname: Song
authors.forename: Austin K
authors.initials: AK
authors.lastname: Mircheff
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schechter
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Yiu
authors.forename: Melvin D
authors.initials: MD
authors.lastname: Trousdale
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications* / Q000276:immunology / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D003607:Dacryocystitis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D004334:Drug Administration Schedule; D015352:Dry Eye Syndromes / Q000209:etiology / Q000276:immunology / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007637:Keratoconjunctivitis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013666:Tears / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine