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Updated: Jul 5, 2026
Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
MCP-1 deficiency delays regression of pathologic retinal neovascularization in a model of ischemic retinopathy
Michael H Davies1, Andrew J Stempel, Michael R Powers
1Department of Pediatrics, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
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.
Insights
Mice lacking MCP-1 showed similar early retinal neovascularization but delayed regression. Reduced macrophages in these mice correlated with less apoptosis and sustained NV, suggesting macrophages promote regression.
Area of Science:
- Ophthalmology
- Immunology
- Vascular Biology
Background:
- Retinal neovascularization (NV) is a hallmark of several vision-threatening diseases.
- Monocyte chemoattractant protein-1 (MCP-1) plays a role in inflammatory processes.
- The role of MCP-1 in the specific context of retinal NV and apoptosis remains to be fully elucidated.
Purpose of the Study:
- To investigate the impact of MCP-1 deficiency on retinal neovascularization (NV) and apoptosis in a mouse model of oxygen-induced retinopathy (OIR).
- To determine the role of MCP-1 in regulating macrophage/microglia infiltration and their function in retinal NV regression.
Main Methods:
- Utilized MCP-1-deficient ((-/-)) and wild-type (C57BL/6) mice in an oxygen-induced retinopathy (OIR) model.
- Assessed retinal vascular development, vaso-obliteration, and preretinal neovascularization (NV) at various postnatal days.
- Quantified macrophage/microglia infiltration using immunostaining (F4/80) and evaluated apoptosis via TUNEL analysis.
Main Results:
- MCP-1(-/-) mice exhibited normal retinal vascular development and similar initial vaso-obliteration compared to controls.
- While early NV (P17) was comparable, MCP-1(-/-) mice showed significantly increased preretinal NV on P21 and P24.
- This increase in NV was associated with reduced F4/80(+) cells and a significant decrease in vascular tuft apoptosis in MCP-1(-/-) mice.
Conclusions:
- MCP-1 deficiency does not affect normal retinal vascularization or initial neovascularization in OIR.
- Absence of MCP-1 leads to delayed regression of retinal NV, linked to reduced macrophage/microglia presence and decreased apoptosis.
- These findings suggest MCP-1 and associated macrophages/microglia are crucial for the regression of retinal neovascularization, potentially via pro-apoptotic mechanisms.
