Toshida Hiroshi, Nguyen Doan H, Beuerman Roger W, Murakami Akira
Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2736-41. doi: 10.1167/iovs.08-1880. Epub 2009 Feb 14.
To evaluate neurologically acute lacrimation caused by cyclosporine (CsA) eyedrops in rabbit.
Normal adult male New Zealand White rabbits and those that underwent parasympathectomy each received a single instillation of 0.1% CsA or vehicle eyedrops. Schirmer tear test (STT) results, flow rate of lacrimal gland (LG) fluid from the excretory lacrimal duct of the main LG, and blink rate (over a 3-minute period) were measured before and after instillation of CsA or vehicle. Light microscopy was performed to examine the main LG in vitro. Protein release from LG fragments was assessed after incubation with CsA for 30 minutes.
In normal rabbits, the STT value and the flow rate of LG fluid were significantly increased after treatment with CsA compared with vehicle (P < 0.05). In contrast, no changes were found in denervated eyes. The blink rate of CsA-treated eyes was significantly higher than that of vehicle-treated eyes in normal rabbits (P < 0.005), whereas that of denervated eyes decreased significantly after CsA instillation compared with before administration (P < 0.005). Light microscopy showed that the cytoplasm of acinar cells was packed with secretory granules in denervated LG tissue 7 days after parasympathectomy. The same finding was observed 3 hours after CsA instillation. CsA had no stimulatory effect on protein release by acinar cells in LG fragments at all concentrations tested.
These results suggest that CsA has no direct effect on tear fluid secretion from the LG in an acute model. Instead, CsA increases reflex tear flow.
评估环孢素（CsA）滴眼液对兔神经源性急性泪液分泌的影响。
正常成年雄性新西兰白兔和接受过交感神经切除术的兔子分别单次滴注0.1% CsA或赋形剂滴眼液。在滴注CsA或赋形剂之前和之后，测量泪液分泌试验（STT）结果、主泪腺排泄泪道的泪腺（LG）液流速以及眨眼频率（3分钟内）。进行光学显微镜检查以体外观察主泪腺。将LG片段与CsA孵育30分钟后评估蛋白质释放情况。
在正常兔子中，与赋形剂相比，用CsA治疗后STT值和LG液流速显著增加（P < 0.05）。相比之下，去神经支配的眼睛未发现变化。在正常兔子中，用CsA治疗的眼睛的眨眼频率显著高于用赋形剂治疗的眼睛（P < 0.005），而与给药前相比，去神经支配的眼睛在滴注CsA后眨眼频率显著降低（P < 0.005）。光学显微镜检查显示，交感神经切除术后7天，去神经支配的LG组织中腺泡细胞的细胞质充满分泌颗粒。在滴注CsA 3小时后也观察到相同的结果。在所有测试浓度下，CsA对LG片段中腺泡细胞的蛋白质释放均无刺激作用。
这些结果表明，在急性模型中，CsA对泪腺泪液分泌无直接影响。相反，CsA增加反射性泪液分泌。
