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Deniz Hos, Anne Kiesewetter, Claus Cursiefen, Sabine A. Eming; CSFR-1+ CX3CR1+ resident corneal macrophages regulate inflammatory corneal hemangiogenesis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):887.
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Aim of this study was to investigate whether resident corneal macrophages are involved in the regulation of inflammatory corneal hem- and lymphangiogenesis.
Resident corneal macrophages were characterized in corneal whole mounts using F4/80, CX3CR1, CCR2, and CSFR-1. The impact of CX3CR1 deficiency and CCR2 deficiency on resident corneal macrophage numbers was analyzed in CX3CR1 knockout mice (CX3CR1-/-) and CCR2 knockout mice (CCR2-/-). In addition, wildtype mice were treated with an antibody directed against CSFR-1 (anti-CSFR-1), and resident corneal macrophage numbers were determined. Furthermore, suture placement was performed in wildtype mice after anti-CSFR-1 treatment and inflammatory corneal hem- and lymphangiogenesis was quantified in whole mounts using CD31 and LYVE-1 after 1 week.
Healthy corneas of wildtype mice contained a significant number of resident F4/80+ macrophages. The majority of resident F4/80+ corneal macrophages were also positive for CX3CR1 and CSFR-1, whereas CCR2 was only expressed by a minority of resident F4/80+ corneal macrophages located in the corneal periphery. CSFR-1 was only expressed by F4/80+ CX3CR1+ macrophages, but not by F4/80+ CCR2+ macrophages. The number of resident F4/80+ corneal macrophages in CX3CR1-/- and CCR2-/- were comparable to wildtype controls. In contrast, treatment with anti-CSFR-1 strongly reduced resident F4/80+ corneal macrophage numbers when compared to isotype treated corneas (mean area covered by F4/80+ macrophages: 16.4% in isotype controls vs. 4.8% in anti-CSFR-1 treated corneas; p<0.01). Importantly, suture placement after anti-CSFR-1 treatment significantly reduced inflammatory corneal hemangiogenesis (mean vascularized area: 22.6% in isotype controls vs. 17.5% in anti-CSFR-1 treated corneas; p=0.03), whereas corneal lymphangiogenesis was not affected (mean vascularized area: 7.0% in isotype controls vs. 7.5% in anti-CSFR-1 treated corneas; p>0.05).
Resident F4/80+ CX3CR1+ corneal macrophages depend on CSFR-1, but not on CX3CR1 or CCR2. Furthermore, resident corneal macrophages significantly contribute to inflammatory corneal hemangiogenesis, but not lymphangiogenesis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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