PURPOSE: 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.
PURPOSE: 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: Jean S Oak; Jonathan A Deane; Michael G Kharas; Ji Luo; Thomas E Lane; Lewis C Cantley; David A Fruman Journal: Proc Natl Acad Sci U S A Date: 2006-10-27 Impact factor: 11.205
Authors: P B Thomas; Z Zhu; S Selvam; D M Samant; D Stevenson; A K Mircheff; J E Schechter; S W Song; M D Trousdale Journal: J Autoimmun Date: 2008-06-04 Impact factor: 7.094
Authors: Jerry Y Niederkorn; Michael E Stern; Stephen C Pflugfelder; Cintia S De Paiva; Rosa M Corrales; Jianping Gao; Karyn Siemasko Journal: J Immunol Date: 2006-04-01 Impact factor: 5.422
Authors: Padmaja B Thomas; Deedar M Samant; Shivaram Selvam; Rui Hua Wei; Yanru Wang; Douglas Stevenson; Joel E Schechter; Florence Apparailly; Austin K Mircheff; Melvin D Trousdale Journal: Invest Ophthalmol Vis Sci Date: 2010-05-26 Impact factor: 4.799
Authors: Marjan Farid; Anshu Agrawal; Daniel Fremgen; Jeremiah Tao; He Chuyi; Anthony B Nesburn; Lbachir BenMohamed Journal: Ocul Immunol Inflamm Date: 2014-12-23 Impact factor: 3.070