MCP-1 Deficiency Delays Regression of Pathologic Retinal Neovascularization in a Model of Ischemic Retinopathy
Open Access
- 1 September 2008
- journal article
- research article
- Published by Association for Research in Vision and Ophthalmology (ARVO) in Investigative Ophthalmology & Visual Science
- Vol. 49 (9), 4195-4202
- https://doi.org/10.1167/iovs.07-1491
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 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.This publication has 57 references indexed in Scilit:
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