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Title: | Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice | Authors: | Song, Y Liao, Y Liu, T Chen, Y Wang, F Zhou, Z Zhang, W Li, J |
Issue Date: | 2024 | Source: | Frontiers in immunology, 2024, v. 15, 1366841 | Abstract: | Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-β-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. Discussion: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD. |
Keywords: | Age-related macular degeneration (AMD) Choroidal neovascularization Inflammation Microglial repopulation PLX3397 |
Publisher: | Frontiers Research Foundation | Journal: | Frontiers in immunology | EISSN: | 1664-3224 | DOI: | 10.3389/fimmu.2024.1366841 | Rights: | © 2024 Song, Liao, Liu, Chen, Wang, Zhou, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The following publication Song Y, Liao Y, Liu T, Chen Y, Wang F, Zhou Z, Zhang W and Li J (2024) Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice. Front. Immunol. 15:1366841 is available at https://doi.org/10.3389/fimmu.2024.1366841. |
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