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SR Planck, TT Nguyen, K Mohs, K Sampath Damador; Mice Deficient in the Chemokine Receptor CXCR2 Have Reduced Neutrophil Infiltration but Not Reduced Neovascularization Following Corneal Injury . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1746.
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Purpose: Members of the IL-8 family of chemokines have been associated with neovascularization as well as chemotaxis of neutrophils. We previously reported that a genetic deficiency in the murine IL-8 receptor homolog (CXCR2) gene had no apparent affect on early vascular changes following central corneal injury by silver nitrate. Very little neovascularization was produced by that injury so we have expanded the study by using an injury method that induces robust vessel growth in genetic controls and by extending the observation period. Methods: BALB/c CXCR2 knockout (KO) mice and heterozygous (het) littermate controls were anesthetized and their corneas injured by a 5-second application of a silver nitrate cautery stick to the central cornea for 5 seconds and a 1-second application to one segment of the limbus and adjacent conjunctiva. 4 to 5 eyes per group were used for histology and sections stained for esterase (PMNs) and F4/80 antigen (macrophages and dendritic cells). Whole-mount and intravital microscopy to monitor neovascularization were also done with 4 to 5 eyes per group. Results: As found with the original injury model, 1 day post injury the CXCR2 knockout mice had dramatically fewer infiltrating PMNs (487 cells/section in het vs 54 cells/section in KO mice, p=0.013) and only a trend toward fewer F4/80+ cells per section (26 in het vs 12 in KO mice, p=0.1). On day 5 post injury, many more F4/80+ cells had infiltrated the corneal stromas, but there was still only a trend for fewer cells per section in the KO mice (153 in het vs.110 in KO, p=0.06). Increased branching of limbal vessels was seen as early as 32 hours after injury. Neovascularization was clearly evident by day 3 in both KO and het mice. Some of the new vessels regress while others continue to grow. Some vessels in the het mice extended halfway to the burn by day 6 and reached the wound in the central cornea by day 15. Vessels in the KO mice tended to grow somewhat faster and were anastomosing in the central cornea by day 15. Conclusion: Although the CXCR2 KO mice had an 89% reduction in the number of infiltrating neutrophils compared to genetic controls, these mice did not display any reduction in the rate or extent of neovascularization. Neither PMNs in the cornea nor ligands for the CXCR2 receptor appear to be essential for the robust neovascularization observed in this model.
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