Opposing Roles of Blood-Borne Monocytes and Tissue-Resident Macrophages in Limbal Stem Cell Damage after Ocular Injury

Limbal stem cell (LSC) deficiency is a frequent and severe complication after chemical injury to the eye. Previous studies have assumed this mediated directly by caustic agent. Here we show that LSC damage occurs through immune mediators, even without direct LSCs. In particular, pH elevation in anterior chamber (AC) causes acute uveal stress, release of inflammatory cytokines at basal limbal tissue, subsequent death. Peripheral C-C chemokine receptor type 2 positive/CX3C motif 1 negative (CCR2+ CX3CR1−) monocytes are key mediators upregulation tumor necrosis factor-alpha (TNF-α) limbus. contrast peripherally derived monocytes, CX3CR1+ CCR2− tissue-resident macrophages protective role, their depletion prior exacerbates loss increases vulnerability TNF-α-mediated apoptosis independently CCR2+ infiltration into tissue. Consistently, repopulation tissue new resident not only restores M2-like phenotype but also suppresses exposure signals. These findings may clinical implications patients with burns or due other conditions.