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

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. PMID: 31783006 [PubMed - as supplied by publisher]
Source: Am J Pathol - Category: Pathology Authors: Tags: Am J Pathol Source Type: research