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Abstract #107730 Published in IGR 23-4
Aryl hydrocarbon receptor dependent anti-inflammation and neuroprotective effects of tryptophan metabolites on retinal ischemia/reperfusion injury
Yang Y; Wang N; Xu L; Liu Y; Huang L; Gu M; Wu Y; Guo W; Sun HCell Death and Disease 2023; 14: 92
Glaucoma is the major cause of irreversible blindness in the world characterized by progressive retinal neurodegeneration, in which local inflammation in retina is involved in persistent loss of retinal ganglion cells (RGCs). In order to explore whether aryl hydrocarbon receptor (AhR) and its agonists tryptophan metabolites are involved in the development of glaucoma, we collected serum and retinas from non-glaucoma controls and patients with glaucoma. RESULTS: showed altered serum tryptophan metabolism and reduced retinal AhR expression in glaucoma patients. We also showed intraperitoneally injection of tryptophan metabolite 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) down-regulated retinal local inflammation and protected RGC apoptosis from retinal ischemia/reperfusion (IR) injury via AhR activation. We further revealed that ITE could inhibit inflammation in BV2 microglia and alleviate the neurotoxicity of microglial conditioned medium to RGCs under IR. Finally, we illustrated the possible mechanism that ITE limited ERK and NFκB dependent microglial inflammation. In summary, these findings suggest the critical role of tryptophan metabolism and retinal AhR signaling in modulating local inflammation mediated by microglia in glaucoma, and provide a novel avenue to targeting the intrinsically altered AhR signaling resulted from disturbed tryptophan metabolism for glaucoma treatment.
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