EXTENDED REPORT

Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats

Keiko Oh-i^*, Hiroshi Keino^*, Hiroshi Goto, Naoyuki Yamakawa, Kouhei Murase, Yoshihiko Usui, Takeshi Kezuka, Jun-ichi Sakai, Masaru Takeuchi and Masahiko Usui

Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan

Correspondence to:
Correspondence to:
Dr H Keino
Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; hirojunharu{at}aol.com

Aim: To determine whether intravitreal injection of tacrolimus suppresses ongoing experimental autoimmune uveoretinitis (EAU) in rats.

Methods: Rats were immunised with interphotoreceptor retinoid-binding protein peptide (R14) and given an intravitreal injection of tacrolimus on day 12 after immunisation. Intraocular inflammation was assessed by slit-lamp biomicroscopy and histopathological examination. Interferon and tumour necrosis factor protein levels in the ocular tissues were measured. Gene expression of chemokines was determined in ocular tissues by reverse transcription-polymerase chain reaction. To evaluate the systemic effect of intravitreal injection of tacrolimus, delayed-type hypersensitivity was measured by ear swelling.

Results: Clinical and pathological scores showed that ocular inflammation of tacrolimus-treated eyes was markedly less than that of vehicle-treated eyes. The amount of interferon and tumour necrosis factor was considerably inhibited in tacrolimus-treated eyes. The gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES) was markedly reduced in tacrolimus-treated eyes. Delayed-type hypersensitivity responses were not impaired in tacrolimus-treated rats.

Conclusions: Intravitreal injection of tacrolimus was highly effective in suppressing the ongoing process of EAU without any side effects on systemic cellular immunity. This treatment may be useful in the management of patients with severe uveitis.

Abbreviations: EAU, experimental autoimmune uveoretinitis; IFN, interferon; MCP-1, monocyte chemoattractant protein-1; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; RANTES, regulated upon activation, normal T cell expressed and secreted; TNF, tumour necrosis factor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Intravitreal anti-inflammatory treatment for uveitis

S Sugita
Br. J. Ophthalmol. 2007 91: 135-136. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Watanabe, T., Keino, H., Sato, Y., Kudo, A., Kawakami, H., Okada, A. A. (2009). High Mobility Group Box Protein-1 in Experimental Autoimmune Uveoretinitis. IOVS 50: 2283-2290 [Abstract] [Full Text]  
• Kowalczuk, L., Touchard, E., Camelo, S., Naud, M.-C., Castaneda, B., Brunel, N., Besson-Lescure, B., Thillaye-Goldenberg, B., Bigey, P., BenEzra, D., de Kozak, Y., Behar-Cohen, F. (2009). Local Ocular Immunomodulation Resulting from Electrotransfer of Plasmid Encoding Soluble TNF Receptors in the Ciliary Muscle. IOVS 50: 1761-1768 [Abstract] [Full Text]  
• Cunningham, M. A., Austin, B. A., Li, Z., Liu, B., Yeh, S., Chan, C.-C., Anglade, E., Velagaleti, P., Nussenblatt, R. B. (2009). LX211 (Voclosporin) Suppresses Experimental Uveitis and Inhibits Human T Cells. IOVS 50: 249-255 [Abstract] [Full Text]  
• Sugita, S (2007). Intravitreal anti-inflammatory treatment for uveitis. Br. J. Ophthalmol. 91: 135-136 [Full Text]