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• W3204484650 abstract "Abstract Limbal stem cell (LSC) deficiency is a frequent and severe complication after chemical injury to the eye. Previous studies have assumed that this is mediated by direct chemical injury. Here we show that LSC loss can occur even without direct chemical injury to LSCs. Elevation of anterior chamber (AC) pH causes acute uveal stress, release of inflammatory cytokines at the basal limbal tissue, and subsequent LSC death. In particular, peripherally-derived CCR2 + CX3CR1 −- monocytes cause upregulation of tumor necrosis factor alpha (TNF-α) at the limbus, causing LSC loss. In contrast to peripherally-derived monocytes, CX3CR1 + CCR2 −- tissue-resident macrophages are protective. Pharmacological depletion of tissue-resident macrophages prior to injury exacerbates LSC loss and increases LSC vulnerability to apoptosis following exposure to TNF-α, despite reduced CCR2 + cell infiltration into the tissue. Consistently, repopulation of the cornea by new tissue-resident macrophages after depletion reverse LSC susceptibility to inflammatory cell death. This findings have important implication in LSC protection after chemical injury. Significance Limbal stem cell (LSC) loss after chemical burn is a significant clinical problem that has long been thought to be the result of direct chemical injury. This study demonstrates the existence of competing inflammatory mechanism responsible for LSC death, mediated by infiltrating peripheral monocytes that antagonize and overcome the protective role of tissue-resident macrophages. Thus, enhancing the role of tissue-resident macrophages while suppressing that of infiltrating monocytes could be a novel therapeutic strategy for LSC survival." @default.
• W3204484650 created "2021-10-11" @default.
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• W3204484650 date "2021-07-26" @default.
• W3204484650 modified "2023-09-27" @default.
• W3204484650 title "Opposing roles of blood-borne monocytes and tissue-resident macrophages in limbal stem cell damage after ocular injury" @default.
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• W3204484650 doi "https://doi.org/10.1101/2021.07.25.453707" @default.
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