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 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.

Effects of atropine on the barrier function of retinal pigment epithelial cells in myopia

“…Retinal detachment is one of the most common complications of high myopia, mainly manifesting as the separation between the neuroepithelial layer and the pigment epithelial layer. The tight junction proteins occludin and ZO-1 in the ciliary body and retina of high myopic eyes are signi cantly down-regulated, which indicates the disruption of the blood-aqueous barrier in highly myopic eyes [14]. With consideration of the morphological changes of RPE-BM layer in myopia and the occurrence of complications in high myopia, RPE-BM barrier function, including tight and adhesion junction, plays an important role in the progression of myopia, especially pathologic one.…”