title: Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Oh-i
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Keino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Kouhei
authors.initials: K
authors.lastname: Murase
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sakai
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Usui
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D005123:Eye / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007267:Injections; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D014822:Vitreous Body
chemical_list: D018925:Chemokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016559:Tacrolimus