title: MCP-1 deficiency delays regression of pathologic retinal neovascularization in a model of ischemic retinopathy.
abstract: OBJECTIVE
  The present study investigates whether retinal neovascularization (NV) and apoptosis are altered in MCP-1-deficient ((-/-)) mice in the OIR model.
  
  
  METHODS
  Postnatal day (P) 7 MCP-1(-/-) and C57BL/6 (B6) mice were exposed to 75% oxygen for 5 days and then recovered in room air. Immunostaining was performed to localize macrophages/microglia within retinal whole mounts and cross-sections. Retinopathy was qualitatively assessed in FITC-dextran-perfused retinas, and preretinal NV was quantified on P17, P21, and P24. TUNEL analysis was used to compare apoptosis between B6 and MCP-1(-/-) mice.
  
  
  RESULTS
  MCP-1(-/-) and B6 mice revealed normal vascular development in room air controls and similar vaso-obliteration in oxygen-exposed mice on P12. MCP-1(-/-) mice exhibited significantly reduced vascular tuft-associated F4/80(+) cells compared with B6 mice. FITC-dextran-perfused retinas exhibited prominent neovascular tufts on P17, and quantification of preretinal nuclei revealed no significant differences between MCP-1(-/-) and B6 mice. In contrast, on P21 and P24, MCP-1(-/-) mice exhibited significant increases in preretinal neovascular nuclei compared with B6 controls. These increases in NV in the MCP-1(-/-) mice were associated with a significant reduction in vascular tuft apoptosis.
  
  
  CONCLUSIONS
  The results demonstrate that the absence of MCP-1 does not alter normal retinal vascular development. Furthermore, MCP-1(-/-) mice exhibit a similar neovascular response on P17. However, the reduction in tuft-associated macrophages/microglia in the MCP-1(-/-) mice correlates with reduced vascular tuft apoptosis and delayed regression of retinal NV. These findings suggest that macrophages/microglia may contribute to tuft regression through their proapoptotic properties.
authors.affiliation: Department of Pediatrics, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Davies
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stempel
authors.forename: Michael R
authors.initials: MR
authors.lastname: Powers
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000172:deficiency* / Q000235:genetics; D003433:Crosses, Genetic; D017931:DNA Primers; D005451:Fluorescein Angiography; D007511:Ischemia / Q000235:genetics*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000235:genetics / Q000517:prevention & control*; D012160:Retina / Q000254:growth & development / Q000502:physiology; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017931:DNA Primers