Macrophage extracellular traps as key mediators of scleral remodeling in myopia induced by hypoxia and activated platelets

High myopia poses a significant public health challenge due to its rising prevalence and the associated risk of vision-threatening complications. Macrophages play a crucial role in myopic changes; however, the underlying mechanisms remain poorly understood. In the present work, we utilized a mouse lens-induced myopia (LIM) model to elucidate the role of macrophages in myopic scleral remodeling through the release of macrophage extracellular traps (METs). Inhibition of scleral MET release, either through genetic knockout or the MET release inhibitor lactoferrin, effectively suppressed LIM-induced myopia progression. We further investigated the factors that trigger MET release in myopic sclera. Our findings demonstrated that scleral hypoxia, in conjunction with hypoxia-activated platelets, induced autophagy in macrophages, leading to the subsequent release of METs. These findings identify a significant therapeutic target for myopia management and suggest lactoferrin as a promising pharmacological candidate for myopia prevention.