Tryptophan and Kynurenine Pathway Metabolites in Animal Models of Retinal and Optic Nerve Damage: Different Dynamics of Changes.

摘要: Kynurenines, products of tryptophan (TRP) metabolism, display neurotoxic (e.g., 3-hydroxykynurenine; 3-HK), or neuroprotective kynurenic acid; KYNA) properties. Imbalance between the enzymes constituting kynurenine pathway (KP) plays a role in several disease, including neurodegeneration. In this study, we track changes concentrations and its selected metabolites after damage to retinal ganglion cells link data with expression KP enzymes. Brown-Norway rats were subjected intravitreal N-methyl-D-aspartate (NMDA) injection partial optic nerve crush (PONC). Retinas collected 2 7 days completion PONC NMDA injection. Concentrations TRP, (KYN), KYNA determined by high performance liquid chromatography (HPLC). Data on gene rat retina extracted from GEO, public microarray experiments database. Two concentration TRP decreased, while KYN increased. At day compared decrease KYN, further reduction observed, but was still elevated when controls. no statistically significant alterations 3-HK observed. higher group than However, both lower. seven 3-HK, higher, whereas declined. vivo showed that lesion affect metabolism via KP. pattern metabolite different depending model. particular, levels decreased elevated. These observations correspond genes encoding assessed transection. After intraorbital downregulation KyatI KyatIII 24 h 3 procedure Kmo transiently upregulated (12 procedures). transsection (IONT) 48 days, downregulated 12, h, 15 days. Collected point conclusion development therapeutic strategies targeting could be beneficial diseases involving