CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety

Cell Discovery · 11 authors, 11 centres

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TL;DR

The study first confirmed an association between high myopia and higher anxiety risk in human patients, and then used a mouse model to demonstrate that CCL2-mediated inflammation and blood-ocular/brain barrier disruption are key mechanisms linking high myopia to anxiety.

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This study combined a human observational investigation with preclinical mouse experiments. Mechanistic studies in a mouse model of high myopia (induced by -10 D lenses) showed that highly myopic visual stimulation increased CCL2 expression in the retina, leading to elevated circulating CCL2 and monocytes. This resulted in increased infiltration of inflammatory monocytes/macrophages into the eyes and anxiety-related brain areas (basolateral amygdala and ventral hippocampus), along with disruption of the blood-ocular barrier and blood-brain barrier. *Ccl2* gene deficiency or CCL2 blockage attenuated these effects and reduced anxiety-like behavior. The authors conclude that CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety, proposing a model where ocular inflammation drives systemic and neuroinflammatory changes. Limitations include the focus on patients with anxiety, the lack of low/moderate myopia groups, and the observational nature of the human data.

STUDY TYPE

other

SPECIALTY

ophthalmology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10497683

CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety

Cell Discovery

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ABSTRACT

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. Subject terms: Innate immunity, Mechanisms of disease

CITATION EXPORT

Xiangjia Zhu, Jiaqi Meng, Chaofeng Han et al.. CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety. Cell Discovery. (2023). https://doi.org/10.1038/s41421-023-00588-2

AUTHORS

11 · 11 CENTRES

Xiangjia Zhu, Jiaqi Meng, Chaofeng Han, Qingfeng Wu, Yu Du, Jiao Qi, Ling Wei, Hao Li, Wenwen He, Keke Zhang, Yi Lu

1Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China
2NHC Key Laboratory of Myopia, Fudan University, Shanghai, China
3Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China
4Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
5State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China
6Department of Histoembryology, Naval Medical University, Shanghai, China
7Shanghai Key Laboratory of Cell Engineering, Naval Medical University, Shanghai, China
8State Key Laboratory of Molecular Development Biology, Chinese Academy of Sciences, Beijing, China
9Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, Beijing, China
10CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China
11Chinese Institute for Brain Research, Beijing, China