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Originally published In Press as doi:10.1167/iovs.08-2649 on January 10, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:2255-2261.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2649
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Suppression of Experimental Autoimmune Uveitis by Angiotensin II Type 1 Receptor Blocker Telmisartan

Yoko Okunuki,1,2 Yoshihiko Usui,1,2 Norihiro Nagai,3 Takeshi Kezuka,1 Susumu Ishida,3 Masaru Takeuchi,1 and Hiroshi Goto1

1From the Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan; and the 3Laboratory of Retinal Cell Biology, Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

PURPOSE. Angiotensin II type 1 receptor (AT1-R) blockers are used widely for the treatment of patients with hypertension. Recent reports have suggested that AT1-R also plays a key role in various inflammatory conditions. The aim of this study was to examine whether blockade of AT1-R is effective in the suppression of murine experimental autoimmune uveoretinitis (EAU).

METHODS. C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein–derived peptide 1–20 (hIRBP-p). Telmisartan, an AT1-R blocker, was administrated daily by intraperitoneal injection. On day 21 after immunization, the severity of EAU was assessed clinically and histopathologically. With the use of flow cytometry, the activation of draining lymph node (LN) cells was assessed by cell proliferation response against hIRBP-p and by the number of CD44high activated CD4+ T cells present. In addition, mRNA expression of ICAM-1, MCP-1, and IFN-{gamma} in the eye was analyzed by reverse-transcriptase PCR, and the number of retinal adherent leukocytes was counted by retinal perfusion labeling.

RESULTS. Telmisartan significantly suppressed EAU clinically and histopathologically. Intraocular mRNA expression of ICAM-1 and MCP-1 was downregulated, and the retinal adherent leukocyte counts were significantly decreased in telmisartan-treated mice compared with vehicle-treated mice. LN cell proliferative responses against hIRBP-p and the number of CD44highCD4+ T cells were remarkably reduced in telmisartan-treated mice.

CONCLUSIONS. Systemic administration of telmisartan significantly suppressed EAU by the inhibition of antigen-specific T-cell activation in the LNs and of leukocyte adhesion in the retina. These results indicate that telmisartan may be a novel therapeutic regimen for patients with endogenous uveitis.




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