Related Experiment Video
Updated: Jan 2, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Effect of Inhibition of Colony-Stimulating Factor 1 Receptor on Choroidal Neovascularization in Mice
Petra Schwarzer1, Despina Kokona1, Andreas Ebneter1
1Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern; and the Department for BioMedical Research, University of Bern, Bern, Switzerland.
Abstract:
Neovascular age-related macular degeneration is one of the leading causes of blindness. Microglia and macrophages play a critical role in choroidal neovascularization (CNV) and may, therefore, be potential targets to modulate the disease course. This study evaluated the effect of the colony-stimulating factor-1 receptor inhibitor PLX5622 on experimental laser-induced CNV. A 98% reduction of retinal microglia cells was observed in the retina 1 week after initiation of PLX5622 treatment, preventing accumulation of macrophages within the laser site and leading to a reduction of leukocytes within the choroid after CNV induction. Mice treated with PLX5622 had a significantly faster decrease of the CNV lesion size, as revealed by in vivo imaging and immunohistochemistry from day 3 to day 14 compared with untreated mice. Several inflammatory modulators, such as chemokine (C-C motif) ligand 9, granulocyte-macrophage colony-stimulating factor, soluble tumor necrosis factor receptor-I, IL-1α, and matrix metallopeptidase-2, were elevated in the acute phase of the disease when microglia were ablated with PLX5622, whereas other cytokines (eg, interferon-γ, IL-4, and IL-10) were reduced. Our results suggest that colony-stimulating factor-1 receptor inhibition may be a novel therapeutic target in patients with neovascular age-related macular degeneration.
Insights
Targeting colony-stimulating factor-1 receptor with PLX5622 significantly reduced choroidal neovascularization (CNV) lesion size by depleting microglia and macrophages. This suggests a novel therapeutic approach for neovascular age-related macular degeneration.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Neovascular age-related macular degeneration (AMD) is a leading cause of vision loss.
- Microglia and macrophages are key players in choroidal neovascularization (CNV) and represent potential therapeutic targets.
Purpose of the Study:
- To evaluate the efficacy of PLX5622, a colony-stimulating factor-1 receptor inhibitor, in a mouse model of laser-induced CNV.
- To investigate the impact of microglia and macrophage depletion on the development and progression of CNV.
Main Methods:
- Administration of PLX5622 to induce microglia depletion.
- Laser-induced CNV model in mice.
- In vivo imaging and immunohistochemistry to assess CNV lesion size and cellular infiltration.
- Analysis of inflammatory mediator expression.
Main Results:
- PLX5622 treatment led to a 98% reduction in retinal microglia.
- PLX5622 prevented macrophage accumulation at the laser site and reduced choroidal leukocytes.
- CNV lesion size significantly decreased in PLX5622-treated mice compared to controls.
- Differential modulation of inflammatory cytokines and matrix metalloproteinases observed.
Conclusions:
- Colony-stimulating factor-1 receptor inhibition effectively reduces experimental CNV by targeting myeloid cells.
- PLX5622 demonstrates therapeutic potential for neovascular AMD.
- Modulation of specific inflammatory pathways is associated with CSF-1R inhibition in CNV.
