CCL2-mediated inflammatory pathogenesis underlies high myopia-related anxiety.
Xiangjia ZhuJiaqi MengChaofeng HanQing-Feng WuYu DuJiao QiLing WeiHao LiWenwen HeKeke ZhangYi LuPublished in: Cell discovery (2023)
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.
Keyphrases
- blood brain barrier
- mouse model
- liver fibrosis
- liver injury
- optic nerve
- magnetic resonance imaging
- bone marrow
- sleep quality
- cerebral ischemia
- drug induced
- dendritic cells
- optical coherence tomography
- end stage renal disease
- endothelial cells
- high fat diet induced
- computed tomography
- type diabetes
- stem cells
- peritoneal dialysis
- immune response
- peripheral blood
- magnetic resonance
- metabolic syndrome
- white matter
- multiple sclerosis