Improvement of lacrimal function by topical application of CyA in murine models of Sjögren's syndrome.
OBJECTIVE
The object of this study was to evaluate improvement of lacrimal gland (LG) function after topical cyclosporin A (CyA).


METHODS
Topical CyA (0.01% and 0.1%) was applied to two mouse models of Sjögren's syndrome, the NFS/sld after thymectomy and the nonobese diabetic (NOD) mouse, and the functional integrity of the lacrimal gland was evaluated by measuring basal and stimulated tear secretion and its histologic integrity by examining it for apoptosis and lymphocyte invasion.


RESULTS
After treatment with CyA at 0.1% in the NFS/sld mice, tear function increased, and there was a decrease in lymphocyte infiltration of the LG and a decrease in apoptotic figures among the acinar cells. In the NOD mice, tear function also improved, but there was no associated decrease in lymphocyte infiltration. However, the expression of Fas ligand (FasL) in NOD mice by infiltrating lymphocytes was suppressed with 0. 1% CyA eye drops.


CONCLUSIONS
CyA appears to improve tear secretion in mouse models of Sjögren's syndrome by preventing lymphocyte-induced apoptosis of acinar cells. In one model this was achieved by preventing lymphocyte infiltration and in the other by reducing expression of FasL expression on infiltrating lymphocytes.
Tsubota
K
K
Department of Ophthalmology and Oral Health Science Center, Tokyo Dental College, Chiba, Japan. tsubota@tdc.ac.jp
Fujita
H
H
Tadano
K
K
Takeuchi
T
T
Murakami
T
T
Saito
I
I
Hayashi
Y
Y
D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013666:Tears / Q000378:metabolism*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D009883:Ophthalmic Solutions; D016572:Cyclosporine