Schwarzer, Petra; Kokona, Despina; Ebneter, Andreas; Zinkernagel, Martin S. (2020). Effect of Inhibition of Colony Stimulating Factor 1 Receptor on Choroidal Neovascularization in Mice. American journal of pathology, 190(2), pp. 412-425. Elsevier 10.1016/j.ajpath.2019.10.011
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Neovascular age-related macular degeneration is one of the leading causes of blindness. Microglia and macrophages play 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 (CSF-1R) inhibitor PLX5622 on experimental laser-induced CNV. A 98% reduction of retinal microglia cells was observed in the retina one 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 to untreated mice. Several inflammatory modulators, such as CCL9, granulocyte-macrophage colony-stimulating factor, ssoluble tumor necrosis factor receptor-I, interleukin-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, interleukin-4, and interleukin-10) were reduced. Our results suggest that CSF-1R inhibition may be a novel therapeutic target in patients with neovascular age-related macular degeneration.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde 04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Kokona, Despina, Ebneter, Andreas, Zinkernagel, Martin Sebastian |
Subjects: |
600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology |
ISSN: |
0002-9440 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Martin S. Zinkernagel |
Date Deposited: |
17 Dec 2019 13:01 |
Last Modified: |
02 Mar 2023 23:32 |
Publisher DOI: |
10.1016/j.ajpath.2019.10.011 |
PubMed ID: |
31783006 |
BORIS DOI: |
10.7892/boris.136320 |
URI: |
https://boris.unibe.ch/id/eprint/136320 |
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