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- W2034124920 abstract "Purpose.: Endothelial precursor cells (EPCs) derived from hematopoietic stem cells (HSCs) have been shown to contribute to choroidal neovascularization by signaling through the SDF-1/CXCR4 axis. In a prevention and treatment/intervention modality of the laser choroidal neovascularization (CNV) model, the efficacy of CXCR4 inhibition on reducing choroidal leakage and angiogenesis was evaluated. Methods.: CNV in rats was generated by focal rupture of Bruch's membrane with an 810-nm diode laser. In the prevention mode, a CXCR4 antagonist (AMD3100) was delivered via an osmotic pump 1 day after laser induction. In the intervention mode, AMD3100 delivery commenced 14 days after laser induction. Inhibition of CXCR4 was determined through leukocyte and SDF-1 actin polymerization blood biomarker assays. Leakage was assessed by fluorescein angiography, and CNV lesion size was quantified after isolectin B4 endothelial cell staining. SU14813, an anti-VEGFR, PDGFR-β, KIT, and FLT3 inhibitor, was also assessed in an intervention study protocol. Results.: Inhibition of CXCR4 was demonstrated by an increase in the number of blood leukocytes, and diminished SDF-1 induced actin polymerization in whole blood. CNV leakage and neovascularization were inhibited when the dose regimen was initiated 1 day after laser-induced CNV induction. AMD3100 did not show efficacy when administered 14 days after lasering. Treatment with SU14813 significantly decreased CNV leakage and lesion size in an intervention modality. Conclusions.: Inhibition of CXCR4 may be useful in preventing neovascularization but does not appear to have an effect on already established angiogenesis. A multiple receptor tyrosine kinase (RTK) inhibitor approach shows promise for the treatment of wet age-related macular degeneration." @default.
- W2034124920 created "2016-06-24" @default.
- W2034124920 creator A5042067726 @default.
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- W2034124920 date "2010-07-01" @default.
- W2034124920 modified "2023-09-27" @default.
- W2034124920 title "Evaluation of CXCR4 Inhibition in the Prevention and Intervention Model of Laser-Induced Choroidal Neovascularization" @default.
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- W2034124920 doi "https://doi.org/10.1167/iovs.09-3802" @default.
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