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J. Zhou, L. Pham, N. Zhang, S. He, M.–A. Gamulescu, C. Spee, S.J. Ryan, D.R. Hinton; Neutrophils Promote Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5297.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To investigate the role of neutrophils in the development of laser induced experimental choroidal neovasculariztion (CNV Methods:Laser induced CNV was performed in adult male C57BL/6J mice. Neutrophil infiltration was evaluated by histology and confocal immunohistology. The expression of neutrophil chemotactic chemokines in the regions of laser injury was determined by quantitative real–time PCR. Animals were treated with NIMP–R14, an anti–murine neutrophil Ab intra peritoneally (i.p.) to deplete neutrophils. The specific neutrophil depletion was confirmed by flow cytometry. The CNV responses were compared between neutropenic and untreated control mice on the basis of fluorescein angiography, CNV lesion volume and lesion histology analysis, and vascular endothelial growth factor (VEGF) expression by ELISA. Expression of VEGF protein by murine neutrophils was evaluated by confocal immunohistochemistry. Results: Neutrophils infiltrated into the sites of laser lesion as early as day 1 post laser injury and peaked at day 3. The neutrophil infiltration correlated with enhanced expression of neutrophil chemotactic chemokine MIP–2 and KC mRNA in the lesions. Administration of NIMP R14 mAb specifically depleted the neutrophils. Fluorescein angiogram (FA), CNV volume analysis, and lesion histology analysis all demonstrated a moderate decrease in the CNV response in neutropenic mice compared to untreated control mice (p < 0.05). The reduction in the CNV response in neutropenic mice was associated with decreased VEGF protein levels in the ocular posterior segment. Murine neutrophils were shown to contain VEGF protein. Conclusions: Neutrophil invasion was part of early inflammatory responses during laser induced CNV. Neutrophil depletion correlated with reduced CNV responses and decreased VEGF protein expression. These data suggest that neutrophils promote the early development of CNV possibly via VEGF secretion
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