Effect of Inhibition of Colony Stimulating Factor 1 Receptor on Choroidal Neovascularization in Mice.

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)

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 and Zinkernagel, Martin

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:

22 Jan 2020 01:32

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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