Tryptophan and Kynurenine Pathway Metabolites in Animal Models of Retinal and Optic Nerve Damage
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Tryptophan and Kynurenine Pathway Metabolites in Animal Models of Retinal and Optic Nerve Damage : Different Dynamics of Changes. / Fiedorowicz, Michal; Choragiewicz, Tomasz; Thaler, Sebastian; Schuettauf, Frank; Nowakowska, Dominika; Wojtunik, Kamila; Reibaldi, Michele; Avitabile, Teresio; Kocki, Tomasz; Turski, Waldemar A; Kaminska, Agnieszka; Grieb, Pawel; Zrenner, Eberhart; Rejdak, Robert; Toro, Mario Damiano.
In: FRONT PHYSIOL, Vol. 10, 2019, p. 1254.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tryptophan and Kynurenine Pathway Metabolites in Animal Models of Retinal and Optic Nerve Damage
T2 - Different Dynamics of Changes
AU - Fiedorowicz, Michal
AU - Choragiewicz, Tomasz
AU - Thaler, Sebastian
AU - Schuettauf, Frank
AU - Nowakowska, Dominika
AU - Wojtunik, Kamila
AU - Reibaldi, Michele
AU - Avitabile, Teresio
AU - Kocki, Tomasz
AU - Turski, Waldemar A
AU - Kaminska, Agnieszka
AU - Grieb, Pawel
AU - Zrenner, Eberhart
AU - Rejdak, Robert
AU - Toro, Mario Damiano
N1 - Copyright © 2019 Fiedorowicz, Choragiewicz, Thaler, Schuettauf, Nowakowska, Wojtunik, Reibaldi, Avitabile, Kocki, Turski, Kaminska, Grieb, Zrenner, Rejdak and Toro.
PY - 2019
Y1 - 2019
N2 - Kynurenines, products of tryptophan (TRP) metabolism, display neurotoxic (e.g., 3-hydroxykynurenine; 3-HK), or neuroprotective (e.g., kynurenic acid; KYNA) properties. Imbalance between the enzymes constituting the kynurenine pathway (KP) plays a role in several disease, including neurodegeneration. In this study, we track changes in concentrations of tryptophan and its selected metabolites after damage to retinal ganglion cells and link this data with expression of KP enzymes. Brown-Norway rats were subjected to intravitreal N-methyl-D-aspartate (NMDA) injection or partial optic nerve crush (PONC). Retinas were collected 2 and 7 days after the completion of PONC or NMDA injection. Concentrations of TRP, kynurenine (KYN), and KYNA were determined by high performance liquid chromatography (HPLC). Data on gene expression in the rat retina were extracted from GEO, public microarray experiments database. Two days after NMDA injection concentration of TRP decreased, while KYN and KYNA increased. At day 7 compared to day 2 decrease of KYN, KYNA and further reduction of TRP concentration were observed, but on day 7 KYN concentration was still elevated when compared to controls. At day 2 and 7 after NMDA injection no statistically significant alterations of 3-HK were observed. TRP and 3-HK concentration was higher in PONC group than in controls. However, both KYN and KYNA were lower. At day seven concentration of TRP, 3-HK, and KYN was higher, whereas concentration of KYNA declined. In vivo experiments showed that retinal damage or optic nerve lesion affect TRP metabolism via KP. However, the pattern of changes in metabolite concentrations was different depending on the model. In particular, in PONC KYNA and KYN levels were decreased and 3-HK elevated. These observations correspond with data on expression of genes encoding KP enzymes assessed after optic nerve crush or transection. After intraorbital optic nerve crush downregulation of KyatI and KyatIII between 24 h and 3 days after procedure was observed. Kmo expression was transiently upregulated (12 h after the procedures). After intraorbital optic nerve transsection (IONT) Kmo expression was upregulated after 48 h and 7 days, KyatI and KyatIII were downregulated after 12, 48 h, 7 days and upregulated after 15 days. Collected data point to the conclusion that development of therapeutic strategies targeting the KP could be beneficial in diseases involving retinal neurodegeneration.
AB - Kynurenines, products of tryptophan (TRP) metabolism, display neurotoxic (e.g., 3-hydroxykynurenine; 3-HK), or neuroprotective (e.g., kynurenic acid; KYNA) properties. Imbalance between the enzymes constituting the kynurenine pathway (KP) plays a role in several disease, including neurodegeneration. In this study, we track changes in concentrations of tryptophan and its selected metabolites after damage to retinal ganglion cells and link this data with expression of KP enzymes. Brown-Norway rats were subjected to intravitreal N-methyl-D-aspartate (NMDA) injection or partial optic nerve crush (PONC). Retinas were collected 2 and 7 days after the completion of PONC or NMDA injection. Concentrations of TRP, kynurenine (KYN), and KYNA were determined by high performance liquid chromatography (HPLC). Data on gene expression in the rat retina were extracted from GEO, public microarray experiments database. Two days after NMDA injection concentration of TRP decreased, while KYN and KYNA increased. At day 7 compared to day 2 decrease of KYN, KYNA and further reduction of TRP concentration were observed, but on day 7 KYN concentration was still elevated when compared to controls. At day 2 and 7 after NMDA injection no statistically significant alterations of 3-HK were observed. TRP and 3-HK concentration was higher in PONC group than in controls. However, both KYN and KYNA were lower. At day seven concentration of TRP, 3-HK, and KYN was higher, whereas concentration of KYNA declined. In vivo experiments showed that retinal damage or optic nerve lesion affect TRP metabolism via KP. However, the pattern of changes in metabolite concentrations was different depending on the model. In particular, in PONC KYNA and KYN levels were decreased and 3-HK elevated. These observations correspond with data on expression of genes encoding KP enzymes assessed after optic nerve crush or transection. After intraorbital optic nerve crush downregulation of KyatI and KyatIII between 24 h and 3 days after procedure was observed. Kmo expression was transiently upregulated (12 h after the procedures). After intraorbital optic nerve transsection (IONT) Kmo expression was upregulated after 48 h and 7 days, KyatI and KyatIII were downregulated after 12, 48 h, 7 days and upregulated after 15 days. Collected data point to the conclusion that development of therapeutic strategies targeting the KP could be beneficial in diseases involving retinal neurodegeneration.
U2 - 10.3389/fphys.2019.01254
DO - 10.3389/fphys.2019.01254
M3 - SCORING: Journal article
C2 - 31632294
VL - 10
SP - 1254
JO - FRONT PHYSIOL
JF - FRONT PHYSIOL
SN - 1664-042X
ER -