Improvement of lacrimal function by topical application of CyA in murine models of Sjögren's syndrome

Kazuo Tsubota, H. Fujita, K. Tadano, Tsutomu Takeuchi, T. Murakami, I. Saito, Y. Hayashi

Research output: Contribution to journalArticle

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Abstract

PURPOSE. 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 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.

Original languageEnglish
Pages (from-to)101-110
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number1
Publication statusPublished - 2001
Externally publishedYes

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Tears
Cyclosporine
Lymphocytes
Lacrimal Apparatus
Inbred NOD Mouse
Fas Ligand Protein
Acinar Cells
Apoptosis
Thymectomy
Ophthalmic Solutions

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Improvement of lacrimal function by topical application of CyA in murine models of Sjögren's syndrome. / Tsubota, Kazuo; Fujita, H.; Tadano, K.; Takeuchi, Tsutomu; Murakami, T.; Saito, I.; Hayashi, Y.

In: Investigative Ophthalmology and Visual Science, Vol. 42, No. 1, 2001, p. 101-110.

Research output: Contribution to journalArticle

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abstract = "PURPOSE. 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 Sj{\"o}gren'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 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 Sj{\"o}gren'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.",
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AU - Tsubota, Kazuo

AU - Fujita, H.

AU - Tadano, K.

AU - Takeuchi, Tsutomu

AU - Murakami, T.

AU - Saito, I.

AU - Hayashi, Y.

PY - 2001

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N2 - PURPOSE. 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 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.

AB - PURPOSE. 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 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.

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