Macrophages promote vasculogenesis of retinal neovascularization in an oxygen-induced retinopathy model in mice.
To investigate the role of macrophages in oxygen-induced retinal neovascularization (NV) in mice, particularly the involvement of bone marrow-derived cells (BMCs) and the underlying mechanisms, BMCs from green fluorescent protein (GFP) transgenic mice were transplanted into postnatal day (P) 1 mice after irradiation. The mice were exposed to 75 % oxygen from P7 to P12 to initiate oxygen-induced retinopathy (OIR). The macrophages were depleted by injection of clodronate-liposomes (lip) intraperitoneally. The eyes were collected at P12 and P17. Retinal flatmounts and histopathological cross-sections were performed to analyze the severity of retinal NV and BMC recruitment. BMCs immunopositive for CD31 (PECAM-1; endothelial cell marker) and α-SMA (smooth muscle cell marker) antigens were detected using a confocal microscope. Expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) mRNA was detected by RT-PCR. The VEGF, SDF-1, CXCR4 and CD45 protein expression was detected by western blot examination. The retinal avascular area in OIR mice at P12 was unaffected after macrophage depletion carried out twice (38.27 ± 1.92 % reduction) using clodronate-lip. The retinal avascular area and the NV area at P17 were reduced after macrophage depletion four times (79.53 ± 1.02 % reduction); these findings were supported by retinal flatmounts and histopathological cross-sections. Macrophage depletion led to significant inhibition of BMC recruitment into the NV tufts at P17, with decreased expression of retinal VEGF, SDF-1, CXCR4 and CD45. The recruited BMCs differentiated primarily into CD31-positive endothelial cells (ECs) and α-SMA-positive smooth muscle cells (SMCs). This study suggested that macrophages promoted the vasculogenesis of retinal NV, particularly the contribution of BMCs in the mouse OIR model, which might be triggered by VEGF and SDF-1 production.
['Gao|Xiang|X|', 'Wang|Yu-Sheng|YS|', 'Li|Xiao-Qin|XQ|', 'Hou|Hui-Yuan|HY|', 'Su|Jing-Bo|JB|', 'Yao|Li-Bo|LB|', 'Zhang|Jian|J|']
D061605:Administration, Intravenous D000818:Animals D000831:Animals, Newborn D001854:Bone Marrow Cells D002454:Cell Differentiation D002465:Cell Movement D004195:Disease Models, Animal D008264:Macrophages D008810:Mice, Inbred C57BL D010100:Oxygen D012160:Retina D015861:Retinal Neovascularization D012178:Retinopathy of Prematurity
Macrophages Retinal neovascularization Oxygen-induced retinopathy Bone marrow-derived cells Vascular endothelial growth factor Stromal cell-derived factor-1