title: Suppression of experimental uveitis by a recombinant adeno-associated virus vector encoding interleukin-1 receptor antagonist.
abstract: OBJECTIVE
  To evaluate the potential of gene therapy with a recombinant adeno-associated virus vector encoding the interleukin-1 receptor antagonist gene (rAAV-IL-1Ra) in the treatment of experimental uveitis.
  
  
  METHODS
  The vitreal cavity of New Zealand white rabbits was injected with rAAV-IL-1Ra (4x10(7) infectious units), and the contralateral eye was injected with the same amount of rAAV-LacZ or PBS as a control. Transgene expression was evaluated by immunohistochemistry, ELISA, and RT-PCR. To evaluate the therapeutic potential of rAAV-IL-1Ra, experimental uveitis was induced by intravitreal injection of IL-1alpha at 10 and 100 days after rAAV-IL-1Ra administration. The effects of rAAV-IL-1Ra on experimental uveitis were investigated using histological and aqueous analysis.
  
  
  RESULTS
  Following intravitreal injection of rAAV-IL-1Ra, transgene expression was found in various cell types of the ocular tissues, such as ciliary epithelial cells, retinal ganglion cells, and retinal pigment epithelial cells. RT-PCR and ELISA showed that the IL-1Ra transgene persisted in the rabbit eye for at least 100 days. Compared with the control eyes, the transgene expression ameliorated experimental uveitis at 10 and 100 days after a single administration of rAAV-IL-1Ra.
  
  
  CONCLUSIONS
  Intravitreal administration of rAAV-IL-1Ra led to sustained human IL-1Ra transgene expression in rabbit eyes for 100 days. The transgene expression suppressed uveitis episodes at 10 and 100 days after rAAV-IL-1Ra injection. Long-term suppression of experimental uveitis could be achieved by gene therapy with rAAV-IL-1Ra.
authors.affiliation: Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Tsai
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Horng
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Wang
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007267:Injections; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019076:Transgenes; D014605:Uveitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein
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