Citation:Tanaka J,Tanaka H,Mizuki N,Nomura E,Ito N,Nomura N,Yamane M,Hida T,Goshima Y,Hatano H,Nakagawa H.Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis.Int J Ophthalmol 2015;8(1):1-10,doi:10.3980/j.issn.2222-3959.2015.01.01
Semaphorin 3A controls allergic and inflammatory responses in experimental allergic conjunctivitis
Received:November 28, 2014  Revised:December 08, 2014
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DOI:10.3980/j.issn.2222-3959.2015.01.01
Key Words:Semaphorin 3A; experimental allergic conjunctivitis; eosinophil infiltration; serum total IgE; cytokines; instillation; subconjunctival administration
Fund Project:A grant-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
                                
AuthorInstitution
Junmi Tanaka 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
Hideo Tanaka Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Nobuhisa Mizuki Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Eiichi Nomura Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Norihiko Ito Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Naoko Nomura Department of Ophthalmology and Visual Science, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
Masayuki Yamane Department of Environmental Immuno-Dermatology, Graduate School of Medicine, Yokohama City University 3-9 Fukuura, Kanazawa-ku Yokohama 236-0004 Japan
Tomonobu Hida Department of Environmental Immuno-Dermatology, Graduate School of Medicine, Yokohama City University 3-9 Fukuura, Kanazawa-ku Yokohama 236-0004 Japan
Yoshio Goshima Department of Environmental Immuno-Dermatology, Graduate School of Medicine, Yokohama City University 3-9 Fukuura, Kanazawa-ku Yokohama 236-0004 Japan
Hiroshi Hatano Hatano Eye Clinic, 438-1 Fujisawa, Fujisawa, Kanagawa-ken 251-0052, Japan
Hisashi Nakagawa Tokushima Eye Clinic, 1-2-14 Fujimi-cho, Higashimurayama, Tokyo 189-0024, Japan
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Abstract:
      AIM: 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.

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