Thomas Padmaja B, Samant Deedar M, Zhu Zejin, Selvam Shivaram, Stevenson Douglas, Wang Yanru, Song Sang W, Mircheff Austin K, Schechter Joel E, Yiu Samuel C, Trousdale Melvin D
Ocular Surface Center, Department of Ophthalmology, Doheny Eye Institute, Los Angeles, CA 90033, USA.
J Ocul Pharmacol Ther. 2009 Jun;25(3):285-92. doi: 10.1089/jop.2008.0138.
To 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.
利用诱导性自身免疫性泪腺炎兔模型评估局部应用环孢素A（CsA）的疗效。
通过将在与从一侧下泪腺（LG）分离的腺泡细胞进行混合细胞反应中激活的自体外周血淋巴细胞注射回供体动物剩余的下泪腺，诱导自身免疫性泪腺炎。评估泪液分泌试验、泪膜破裂时间和孟加拉玫瑰红染色。对已发病的动物每天局部应用CsA或Endura两次，持续5个月。
未经治疗时，泪液分泌和泪膜稳定性在6个月内均异常，眼表缺陷的明显体征清晰可见。在泪腺中观察到严重的免疫细胞浸润。长期应用CsA治疗仅使泪液分泌略有增加，但泪腺组织病理学的严重程度明显降低。泪腺中CD4(+) T细胞浸润减少，MHC II类表达细胞的浸润也减少。对于Endura治疗组，泪液分泌未改善，孟加拉玫瑰红评分仍较高，组织病理学显示浸润与未治疗组相当，但在研究结束时泪膜破裂时间确实有所改善。
自身免疫性泪腺炎兔模型在疾病诱导6个月后出现慢性干眼病体征。CsA治疗使泪液分泌略有改善，泪腺中CD4(+) T细胞浸润显著减少。这表明一些干燥综合征患者可能从长期CsA治疗中获益。
