PMID- 16987901 OWN - NLM STAT- MEDLINE DCOM- 20070220 LR - 20181113 IS - 0007-1161 (Print) IS - 1468-2079 (Electronic) IS - 0007-1161 (Linking) VI - 91 IP - 2 DP - 2007 Feb TI - Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats. PG - 237-42 AB - 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 gamma and tumour necrosis factor alpha 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 gamma and tumour necrosis factor alpha 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. FAU - Oh-i, Keiko AU - Oh-i K AD - Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. FAU - Keino, Hiroshi AU - Keino H FAU - Goto, Hiroshi AU - Goto H FAU - Yamakawa, Naoyuki AU - Yamakawa N FAU - Murase, Kouhei AU - Murase K FAU - Usui, Yoshihiko AU - Usui Y FAU - Kezuka, Takeshi AU - Kezuka T FAU - Sakai, Jun-Ichi AU - Sakai J FAU - Takeuchi, Masaru AU - Takeuchi M FAU - Usui, Masahiko AU - Usui M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060920 PL - England TA - Br J Ophthalmol JT - The British journal of ophthalmology JID - 0421041 RN - 0 (Chemokines) RN - 0 (Immunosuppressive Agents) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) RN - WM0HAQ4WNM (Tacrolimus) SB - IM CIN - Br J Ophthalmol. 2007 Feb;91(2):135-6. PMID: 17244658 MH - Animals MH - Autoimmune Diseases/*drug therapy/immunology/metabolism MH - Cells, Cultured MH - Chemokines/biosynthesis/genetics MH - Eye/metabolism MH - Female MH - Gene Expression Regulation/drug effects MH - Hypersensitivity, Delayed MH - Immunity, Cellular/drug effects MH - Immunosuppressive Agents/administration & dosage/adverse effects/*therapeutic use MH - Injections MH - Interferon-gamma/biosynthesis MH - Macrophages/drug effects/metabolism MH - RNA, Messenger/genetics MH - Rats MH - Rats, Inbred Lew MH - Retinitis/*drug therapy/immunology/metabolism MH - Tacrolimus/administration & dosage/*therapeutic use/toxicity MH - Treatment Outcome MH - Tumor Necrosis Factor-alpha/biosynthesis MH - Uveitis/*drug therapy/immunology/metabolism MH - Vitreous Body PMC - PMC1857637 COIS- Competing interests: None. EDAT- 2006/09/22 09:00 MHDA- 2007/02/21 09:00 PMCR- 2010/02/01 CRDT- 2006/09/22 09:00 PHST- 2006/09/22 09:00 [pubmed] PHST- 2007/02/21 09:00 [medline] PHST- 2006/09/22 09:00 [entrez] PHST- 2010/02/01 00:00 [pmc-release] AID - bjo.2006.103168 [pii] AID - bj103168 [pii] AID - 10.1136/bjo.2006.103168 [doi] PST - ppublish SO - Br J Ophthalmol. 2007 Feb;91(2):237-42. doi: 10.1136/bjo.2006.103168. Epub 2006 Sep 20.