CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety

Cell Discov. 2023 Sep 12;9(1):94. doi: 10.1038/s41421-023-00588-2.

Xiangjia Zhu ^# ¹ ² ³ ⁴ ⁵, Jiaqi Meng ^# ⁶ ⁷ ⁸ ⁹, Chaofeng Han ¹⁰ ¹¹, Qingfeng Wu ¹² ¹³ ¹⁴ ¹⁵, Yu Du ⁶ ⁷ ⁸ ⁹, Jiao Qi ⁶ ⁷ ⁸ ⁹, Ling Wei ⁶ ⁷ ⁸ ⁹, Hao Li ⁶ ⁷ ⁸ ⁹, Wenwen He ⁶ ⁷ ⁸ ⁹, Keke Zhang ⁶ ⁷ ⁸ ⁹, Yi Lu ¹⁶ ¹⁷ ¹⁸ ¹⁹

Affiliations

1 Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. [email protected].
2 NHC Key Laboratory of Myopia, Fudan University, Shanghai, China. [email protected].
3 Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. [email protected].
4 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. [email protected].
5 State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. [email protected].
6 Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
7 NHC Key Laboratory of Myopia, Fudan University, Shanghai, China.
8 Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.
9 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.
10 Department of Histoembryology, Naval Medical University, Shanghai, China. [email protected].
11 Shanghai Key Laboratory of Cell Engineering, Naval Medical University, Shanghai, China. [email protected].
12 State Key Laboratory of Molecular Development Biology, Chinese Academy of Sciences, Beijing, China.
13 Institute of Genetics and Developmental Biology, University of Chinese Academy of Sciences, Beijing, China.
14 CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, China.
15 Chinese Institute for Brain Research, Beijing, China.
16 Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. [email protected].
17 NHC Key Laboratory of Myopia, Fudan University, Shanghai, China. [email protected].
18 Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. [email protected].
19 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. [email protected].
# Contributed equally.

PMID: 37699875 DOI: 10.1038/s41421-023-00588-2

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.

Products

Cat. No.

Product Name

Description

Target

Research Area
HY-15418

RS 504393

99.43%, CCR2 Antagonist

CCR

Inflammation/Immunology; Endocrinology

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