MCP-1 deficiency delays regression of pathologic retinal neovascularization in a model of ischemic retinopathy

Michael H. Davies, Andrew J. Stempel, Michael R. Powers

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

PURPOSE. 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 pre-retinal 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.

Original languageEnglish (US)
Pages (from-to)4195-4202
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number9
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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