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Updated: May 31, 2026
The Corneal Micropocket Assay: A Model of Angiogenesis in the Mouse Eye
Published on: August 16, 2014
Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model
Beatrice Bourghardt Peebo1, Per Fagerholm, Catharina Traneus-Röckert
1Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden.
Abstract:
In this study, we introduce a technique for repeated, microscopic observation of single regressing capillaries in vivo in inflamed murine corneas. Natural capillary regression was initiated by removal of inflammatory stimulus during an active pro-angiogenic phase, while the additional impact of anti-angiogenic treatment with triamcinolone or bevazicumab was investigated. Capillaries regressed naturally within 1 week and treatments did not further enhance the natural regression. Morphologically, early-phase regression was characterized by significant lumen narrowing and a significant reduction in CD11b+ myeloid cell infiltration of the extracellular matrix. By 1 week, vascular remodeling occurred concomitant with CD11b+CD68+KiM2R+ mature macrophage localization on capillary walls. Empty conduits without blood flow, positive for collagen IV and devoid of vascular endothelium and pericytes, were apparent in vivo and by 3 weeks were more numerous than perfused capillaries. By 3 weeks, macrophages aggregated around remaining perfused capillaries and were observed in apposition with degrading capillary segments. Abrupt termination of capillary sprouting in our regression model further revealed vascular endothelial abandonment of sprout tips and perfused capillary loop formation within a single angiogenic sprout, possibly as an intussusceptive response to cessation of the stimulus. Finally, we observed lumen constriction and macrophage localization on capillary walls in vivo in a clinical case of corneal capillary regression that paralleled findings in our murine model.
Insights
This study reveals how blood capillaries naturally regress in inflamed corneas, showing that myeloid cells and macrophages play key roles in this vascular remodeling process.
Area of Science:
- Ophthalmology
- Angiogenesis Research
- Vascular Biology
Background:
- Corneal neovascularization is a hallmark of ocular inflammation.
- Understanding capillary regression is crucial for developing anti-angiogenic therapies.
- Existing models lack detailed in vivo observation of natural capillary regression.
Purpose of the Study:
- To develop and utilize a technique for repeated, microscopic observation of single regressing capillaries in vivo.
- To investigate natural capillary regression in inflamed murine corneas.
- To assess the impact of anti-angiogenic treatments on capillary regression.
Main Methods:
- Developed a technique for repeated, in vivo microscopic observation of single capillaries.
- Induced capillary regression by removing inflammatory stimuli in murine corneas.
- Administered anti-angiogenic treatments (triamcinolone, bevacizumab).
- Analyzed morphological changes, myeloid cell infiltration, and macrophage localization.
Main Results:
- Capillaries regressed naturally within 1 week; treatments did not enhance regression.
- Early regression involved lumen narrowing and reduced myeloid cell infiltration.
- Mature macrophages localized on capillary walls during remodeling.
- Empty, collagen IV-positive conduits replaced perfused capillaries.
- Vascular endothelial cells abandoned sprout tips, forming loops, suggesting intussusceptive repair.
Conclusions:
- Natural capillary regression is a complex process involving lumen narrowing, myeloid cell dynamics, and macrophage involvement.
- The murine model effectively mimics corneal capillary regression observed in clinical cases.
- Anti-angiogenic drugs did not significantly alter the natural regression timeline in this model.
