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Originally published In Press as doi:10.1167/iovs.08-1880 on February 14, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:2736-2741.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-1880
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Neurologic Evaluation of Acute Lacrimomimetic Effect of Cyclosporine in an Experimental Rabbit Dry Eye Model

Hiroshi Toshida,1 Doan H. Nguyen,2 Roger W. Beuerman,3 and Akira Murakami1

1From the Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan; 2LSU Eye Center, Lion’s Eye Research Laboratories, Laboratory for the Molecular Biology of the Ocular Surface, LSU Health Sciences Center, New Orleans, Louisiana; and 3Singapore Eye Research Institute, Singapore.

PURPOSE. To evaluate neurologically acute lacrimation caused by cyclosporine (CsA) eyedrops in rabbit.

METHODS. 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.

RESULTS. 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.

CONCLUSIONS. 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.






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