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Laboratory science - Extended reports
Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats
  1. Keiko Oh-i*,
  2. Hiroshi Keino*,
  3. Hiroshi Goto,
  4. Naoyuki Yamakawa,
  5. Kouhei Murase,
  6. Yoshihiko Usui,
  7. Takeshi Kezuka,
  8. Jun-ichi Sakai,
  9. Masaru Takeuchi,
  10. Masahiko Usui
  1. Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
  1. 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

Abstract

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 γ and tumour necrosis factor α 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 γ and tumour necrosis factor α 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.

  • 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

https://doi.org/10.1136/bjo.2006.103168

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    Footnotes

    • ↵* These authors contributed equally to this study.

    • Published Online First 20 September 2006

    • Funding: This work was supported by Grant-in-Aid 17791258 for Scientific Research from the Japan Society for the Promotion of Science.

    • Competing interests: None.

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