CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety
Abstract High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic p...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-09-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-023-00588-2 |
| _version_ | 1797453966703853568 |
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| author | Xiangjia Zhu Jiaqi Meng Chaofeng Han Qingfeng Wu Yu Du Jiao Qi Ling Wei Hao Li Wenwen He Keke Zhang Yi Lu |
| author_facet | Xiangjia Zhu Jiaqi Meng Chaofeng Han Qingfeng Wu Yu Du Jiao Qi Ling Wei Hao Li Wenwen He Keke Zhang Yi Lu |
| author_sort | Xiangjia Zhu |
| collection | DOAJ |
| description | Abstract High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic patients exhibit greater anxiety, accompanied by higher CC chemokine ligand 2 (CCL2) and monocyte levels in the blood. Similar findings are found in the mouse model of high myopia. Mechanistic evaluations using GFP-positive bone marrow chimeric mice, parabiotic mouse model, enhanced magnetic resonance imaging, etc., show that highly myopic visual stimulation increases CCL2 expression in eyes, aggravates monocyte/macrophage infiltration into eyes and brains, and disrupts blood–ocular barrier and blood–brain barrier of mice. Conversely, Ccl2-deficient highly myopic mice exhibit attenuated ocular and brain infiltration of monocytes/macrophages, reduced disruption of the blood–ocular barrier and blood–brain barrier, and less anxiety. Substantial alleviation of high myopia-related anxiety can also be achieved with the administration of CCL2-neutralizing antibodies. Our results establish the association between high myopia and anxiety, and implicate the CCL2-mediated inflammatory pathogenesis as an underlying mechanism. |
| first_indexed | 2024-03-09T15:29:33Z |
| format | Article |
| id | doaj.art-bb7cbd1decf24befa1f27b09bec486a4 |
| institution | Directory Open Access Journal |
| issn | 2056-5968 |
| language | English |
| last_indexed | 2024-03-09T15:29:33Z |
| publishDate | 2023-09-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj.art-bb7cbd1decf24befa1f27b09bec486a42023-11-26T12:19:28ZengNature Publishing GroupCell Discovery2056-59682023-09-019111810.1038/s41421-023-00588-2CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxietyXiangjia Zhu0Jiaqi Meng1Chaofeng Han2Qingfeng Wu3Yu Du4Jiao Qi5Ling Wei6Hao Li7Wenwen He8Keke Zhang9Yi Lu10Department of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Histoembryology, Naval Medical UniversityState Key Laboratory of Molecular Development Biology, Chinese Academy of SciencesDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityDepartment of Ophthalmology, Eye & ENT Hospital, Fudan UniversityAbstract High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic patients exhibit greater anxiety, accompanied by higher CC chemokine ligand 2 (CCL2) and monocyte levels in the blood. Similar findings are found in the mouse model of high myopia. Mechanistic evaluations using GFP-positive bone marrow chimeric mice, parabiotic mouse model, enhanced magnetic resonance imaging, etc., show that highly myopic visual stimulation increases CCL2 expression in eyes, aggravates monocyte/macrophage infiltration into eyes and brains, and disrupts blood–ocular barrier and blood–brain barrier of mice. Conversely, Ccl2-deficient highly myopic mice exhibit attenuated ocular and brain infiltration of monocytes/macrophages, reduced disruption of the blood–ocular barrier and blood–brain barrier, and less anxiety. Substantial alleviation of high myopia-related anxiety can also be achieved with the administration of CCL2-neutralizing antibodies. Our results establish the association between high myopia and anxiety, and implicate the CCL2-mediated inflammatory pathogenesis as an underlying mechanism.https://doi.org/10.1038/s41421-023-00588-2 |
| spellingShingle | Xiangjia Zhu Jiaqi Meng Chaofeng Han Qingfeng Wu Yu Du Jiao Qi Ling Wei Hao Li Wenwen He Keke Zhang Yi Lu CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety Cell Discovery |
| title | CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety |
| title_full | CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety |
| title_fullStr | CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety |
| title_full_unstemmed | CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety |
| title_short | CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety |
| title_sort | ccl2 mediated inflammatory pathogenesis underlies high myopia related anxiety |
| url | https://doi.org/10.1038/s41421-023-00588-2 |
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