June 1994
Volume 35, Issue 7
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Articles  |   June 1994
The role of macrophages in the pathogenesis of HSV-1 induced chorioretinitis in BALB/c mice.
Author Affiliations
  • A Berra
    Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
  • A Rodriguez
    Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
  • A Heiligenhaus
    Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
  • B Pazos
    Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
  • N Van Rooijen
    Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
  • C S Foster
    Hilles Immunology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
Investigative Ophthalmology & Visual Science June 1994, Vol.35, 2990-2998. doi:
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    • Get Citation

      A Berra, A Rodriguez, A Heiligenhaus, B Pazos, N Van Rooijen, C S Foster; The role of macrophages in the pathogenesis of HSV-1 induced chorioretinitis in BALB/c mice.. Invest. Ophthalmol. Vis. Sci. 1994;35(7):2990-2998.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

PURPOSE: To examine the effects of modification of immune effector cells, including macrophages, in the pathogenesis of herpes simplex virus retinitis in BALB/c mice. METHODS: Two intravitreal injections (2 microliters each) of anti-CD11b monoclonal antibody (mAb) [13 micrograms/microliters] were administered to the contralateral eyes of 10 BALB/c mice on days 6 and 8 after HSV inoculation into the right anterior chamber (AC) with HSV-1. A control group consisted of mice injected with anti-HLA-DR mAb in the same fashion. Specific macrophage depletion was performed in an additional group of 12 BALB/c mice by intravenous (i.v.) injection of dichloromethylene diphosphonate (Cl2MDP)-liposomes 7 days before AC HSV-1 inoculation into the eye. Control group consisted of mice receiving i.v. PBS-liposomes. Mice were clinically observed for 14 days postinfection, and the incidence of chorioretinal disease was confirmed by histopathologic studies. RESULTS: Intravitreal injections of anti-CD11b mAb produced a dramatic suppression of the contralateral retinal necrosis (2 of 10 mice) compared to 9 of 10 controls receiving an irrelevant antibody therapy (P < 0.05). Mice treated with i.v. Cl2MDP-liposomes also showed a significant inhibition of the development of contralateral chorioretinitis, with only 3 of 12 mice developing retinal disease compared to 9 of 12 mice from the control group (P < 0.05). FACS analysis performed on peripheral blood and spleen cells showed a significant depletion of Mac-1+ cells of Cl2MDP-liposome-treated but not of PBS-liposome-treated mice (controls). CONCLUSION: Intravitreal anti-CD11b mAb therapy, a broadly directed depletion strategy against many effector cells (macrophages, granulocytes, natural killer cells, and even cytotoxic T-cells) was most efficient in suppressing the HSV-1 induced contralateral disease. A more specific technique (i.v. Cl2MDP-liposome therapy) to deplete macrophages also produced a significant inhibition of HSV-1 induced contralateral chorioretinitis. These findings suggest that macrophages are important participants in the effector phase of the destructive inflammatory immune response induced by HSV-1 in the eye.

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