CSF1R blockade induces macrophage ablation and results in mouse choroidal vascular atrophy and RPE disorganization
- National Eye Institute, NIH, United States
Abstract
The choroid, which provides vascular supply to the outer retina, demonstrates progressive degeneration in aging and age-related macular degeneration (AMD). However mechanisms that maintain or compromise choroidal homeostasis are obscure. We discovered that the ablation of choroidal macrophages via CSF1R blockade was associated with choroidal vascular atrophy and retinal pigment epithelial (RPE) changes including structural disruption, downregulation of visual cycle genes, and altered angiogenic factor expression. Suspending CSF1R blockade following ablation enabled spontaneous macrophage regeneration, which fully restored original macrophage distributions and morphologies. Macrophage regeneration was accompanied by arrested vascular degeneration and ameliorated pathological RPE alterations. These findings suggest that choroidal macrophages play a previously unappreciated trophic role in maintaining choroidal vasculature and RPE cells, implicating insufficiency in choroidal macrophage function as a factor in aging- and AMD-associated pathology. Modulating macrophage function may constitute a strategy for the therapeutic preservation of the choroid and RPE in age-related retinal disorders.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
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Author details
Funding
National Eye Institute (Intramural Research Program)
- Xiao Yang
- Lian Zhao
- Maria M Campos
- Mones Abu-Asab
- Davide Ortolan
- Nathan Hotaling
- Kapil Bharti
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (NEI-665) of the National Eye Institute.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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CSF1R blockade induces macrophage ablation and results in mouse choroidal vascular atrophy and RPE disorganization
eLife 9:e55564.
https://doi.org/10.7554/eLife.55564
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