title: Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis.
abstract: OBJECTIVE
  To assess the efficacy of topical Semaphorin-3A (SEMA3A) in the treatment of allergic conjunctivitis.
  
  
  METHODS
  Experimental allergic conjunctivitis (EAC) mice model induced by short ragweed pollen (SRW) in 4-week-old of BALB/c mice, mice were evaluated using haematoxylin and eosin (H&E) staining, immunofluorescence and light microscope photographs. Early phase took the samples in 24h after instillation and late phase took the samples between 4 to 14d after the start of treatment. The study use of topical SEMA3A (10 U, 100 U, 1000 U) eye drops and subconjunctival injection of SEMA3A with same concentration. For comparison, five types of allergy eyedrops were quantified using clinical characteristics.
  
  
  RESULTS
  Clinical score of composite ocular symptoms of the mice treated with SEMA3A were significantly decreased both in the immediate phase and the late phase compared to those treated with commercial ophthalmic formulations and non-treatment mice. SEMA3A treatment attenuates infiltration of eosinophils entering into conjunctiva in EAC mice. The score of eosinophil infiltration in the conjunctiva of SEMA3A 1000 U-treated group were significantly lower than low-concentration of SEMA3A treated groups and non-treated group. SEMA3A treatment also suppressed T-cell proliferation in vitro and decreased serum total IgE levels in EAC mice. Moreover, Treatment of SEMA3A suppressed Th2-related cytokines (IL-5, IL-13 and IL-4) and pro-inflammatory cytokines (IFN-γ, IL-17 and TNF-α) release, but increased regulatory cytokine IL-10 concentration in the conjunctiva of EAC mice.
  
  
  CONCLUSIONS
  SEMA3A as a biological agent, showed the beneficial activity in ocular allergic processes with the less damage to the intraocular tissue. It is expected that SEMA3A may be contributed in patients with a more severe spectrum of refractory ocular allergic diseases including allergic conjunctivitis in the near future.
authors.affiliation: Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan ; Department of Ophthalmology, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Junmi
authors.initials: J
authors.lastname: Tanaka
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Mizuki
authors.affiliation: Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nomura
authors.affiliation: Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ito
authors.affiliation: Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Nomura
authors.affiliation: Department of Environmental Immuno-Dermatology, Graduate School of Medicine, Yokohama City University 3-9 Fukuura, Kanazawa-ku Yokohama 236-0004 Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamane
authors.affiliation: Department of Environmental Immuno-Dermatology, Graduate School of Medicine, Yokohama City University 3-9 Fukuura, Kanazawa-ku Yokohama 236-0004 Japan.
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hida
authors.affiliation: Department of Environmental Immuno-Dermatology, Graduate School of Medicine, Yokohama City University 3-9 Fukuura, Kanazawa-ku Yokohama 236-0004 Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: Hatano Eye Clinic, 438-1 Fujisawa, Fujisawa, Kanagawa-ken 251-0052, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatano
authors.affiliation: Tokushima Eye Clinic, 1-2-14 Fujimi-cho, Higashimurayama, Tokyo 189-0024, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nakagawa
keywords: Semaphorin 3A; cytokines; eosinophil infiltration; experimental allergic conjunctivitis; instillation; serum total IgE; subconjunctival administration