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Hem Raj Gurung, Daniel J Carr; Dexamethasone suppresses HSV-1- induced corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1853.
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© ARVO (1962-2015); The Authors (2016-present)
Herpes simplex virus type 1 (HSV-1) infection of murine cornea induces lymphatic vessel genesis (lymphangiogenesis) through the production of VEGFA by epithelial cells acting through a VEGFR2- dependent pathway. Lymphangiogenesis progresses and is maintained well past the resolution of infection (> 30 days post infection, pi). The present study was undertaken to identify the contribution of cells and pro-angiogenic factors that promote lymphangiogenesis past virus clearance.
C57BL6/J mice were infected with 1,000 plaque forming units (PFU) of HSV-1 per eye. Ten mg/kg dexamethasone (DEX) or vehicle was administered by intraperitoneal injection at day 10 pi. Mice were euthanized at day 14 and day 30 pi and the corneas were removed. Corneal lymphatic vessels (LYVE-1+) and blood vessels (CD31+) were visualized by confocal microscopy following immunohistochemical staining. Infiltrating leukocyte populations were assessed by flow cytometry of corneal single-cell suspensions. Pro-angiogenic protein levels were determined by bioplex multiplex array or ELISA.
A single bolus of DEX at day 10 pi resulted in a significant reduction of blood vessel but not lymphatic vessel development in the cornea at day 14 pi. When DEX-treated mice were euthanized at day 30 pi, there was a remarkable reduction of both blood and lymphatic vessel development into the cornea compared to vehicle-treated control mice. Flow cytometry analysis revealed fewer neutrophils and CD4+ T cells in the corneas of the animals that received DEX with no apparent impact on macrophages and CD8+ T cells compared to vehicle-treated controls at day 14 and day 30 pi. There was a significant decrease in IL-6 and hepatocyte growth factor (HGF) levels at day 14 pi in the corneas of animals that received DEX relative to vehicle-treated controls.
A single bolus of DEX at the time of HSV-1 clearance completely reverses the incidence of angiogenesis in the cornea of mice. This process may involve IL-6 and/or HGF as well as neutrophils and/or CD4+ T cells.
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