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Y. Okunuki, Y. Usui, N. Nagai, T. Kezuka, M. Takeuchi, S. Ishida, H. Goto; Suppression of Experimental Autoimmune Uveoretinaitis by Blocking Angiotensin II type 1 Receptor. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4769. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Angiotensin II type 1 receptor (AT1-R) blockers are widely used for treatment for patients with hypertension. In addition to its blood pressure controling effect, recent reports have suggested that AT1-R plays a key role in various inflammatory conditions. We planned this study to examine whether blockade of AT1-R is effective in suppression of experimental autoimmue uveoretinitis (EAU).
C57BL/6 mice were immunized with interphotoreceptor retinoid binding protein derived peptide 1-20 (IRBP-p). From day -1 to the day before sacrifice, one of the AT1-R blockers, telmisartan, or vehicle was administrated intraperitoneally. On day 21 after immunization, severity of EAU was assessed clinically and histopathologically. Activation of draining lymph nodes (LNs) was assessed by cell proliferation response against restimulation with IRBP-p and by positive rate of CD44high activated CD4-positive T cells using flow cytometry. Intraocular mRNA production was analyzed by RT-PCR. Retinal adherent leukocytes number was counted by retinal perfusion labeling on day 7 after immunisation.
2.5 mg/kg of telmisartan administration remarkably suppressed EAU clinically (p<0.05) and histopathologically (p<0.05). The retinal adherent leukocyte counts were significantly suppressed in telmisartan-treated mice (47.2/retina) compared to vehicle-treated mice (24.6/retina) (p<0.01). Proliferative responses of draining LN cells against restimilation with IRBP-p were suppressed in telmisartan-treated mice (p<0.01). Moreover, CD4-positive T cells in draining LN cells of 19.6% in telmisartan-treated mice and 22.4% in vehicle-treated mice were CD44high (p<0.01). Intraocular expression of ICAM-1 and MCP-1 were suppressed in telmisartan-treated mice in mRNA levels.
Systemic administration of AT1-R blocker, telmisartan, significantly suppressed EAU by inhibiting activation of draining LN cells and the production of inflammatory chemokines in the eye. These results indicate that telmisartan could be one of the new therapeutic regimens for endogenic uveitis.
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