Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma

Int J Mol Sci. 2021 Jan 21;22(3):1039. doi: 10.3390/ijms22031039.

Abstract

Background: It has been shown that a possible pathogenetic mechanism of neurodegeneration in the mouse model of glaucoma (DBA/2J) may be an alteration of kynurenic acid (KYNA) in the retina. This study aimed to verify the hypothesis that alterations of tryptophan (TRP) metabolism in DBA/2J mice is not limited to the retina.

Methods: Samples of the retinal tissue and serum were collected from DBA/2J mice (6 and 10 months old) and control C57Bl/6 mice of the same age. The concentration of TRP, KYNA, kynurenine (KYN), and 3-hydroxykynurenine (3OH-K) was measured by HPLC. The activity of indoleamine 2,3-dioxygenase (IDO) was also determined as a KYN/TRP ratio.

Results: TRP, KYNA, L-KYN, and 3OH-K concentration were significantly lower in the retinas of DBA/2J mice than in C57Bl/6 mice. 3OH-K concentration was higher in older mice in both strains. Serum TRP, L-KYN, and KYNA concentrations were lower in DBA/2J than in age-matched controls. However, serum IDO activity did not differ significantly between compared groups and strains.

Conclusions: Alterations of the TRP pathway seem not to be limited to the retina in the murine model of hereditary glaucoma.

Keywords: DBA/2J; glaucoma; kynurenine pathway; retina.

MeSH terms

  • Animals
  • Biomarkers
  • Disease Models, Animal
  • Disease Susceptibility
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / metabolism*
  • Glaucoma / diagnosis
  • Glaucoma / genetics*
  • Glaucoma / metabolism*
  • Kynurenic Acid / metabolism
  • Kynurenine / analogs & derivatives
  • Kynurenine / metabolism
  • Magnetic Resonance Imaging
  • Metabolic Networks and Pathways*
  • Mice
  • Retina
  • Species Specificity
  • Tryptophan / metabolism*

Substances

  • Biomarkers
  • 3-hydroxykynurenine
  • Kynurenine
  • Tryptophan
  • Kynurenic Acid