Metabolomic changes in the mouse retina after optic nerve injury

Kota Sato, Daisuke Saigusa, Ritsumi Saito, Amane Fujioka, Yurika Nakagawa, Koji M. Nishiguchi, Taiki Kokubun, Ikuko N. Motoike, Kazuichi Maruyama, Kazuko Omodaka, Yukihiro Shiga, Akira Uruno, Seizo Koshiba, Masayuki Yamamoto, Toru Nakazawa

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

In glaucoma, although axonal injury drives retinal ganglion cell (RGC) death, little is known about the underlying pathomechanisms. To provide new mechanistic insights and identify new biomarkers, we combined latest non-targeting metabolomics analyses to profile altered metabolites in the mouse whole retina 2, 4, and 7 days after optic nerve crush (NC). Ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry and liquid chromatography Fourier transform mass spectrometry covering wide spectrum of metabolites in combination highlighted 30 metabolites that changed its concentration after NC. The analysis displayed similar changes for purine nucleotide and glutathione as reported previously in another animal model of axonal injury and detected multiple metabolites that increased after the injury. After studying the specificity of the identified metabolites to RGCs in histological sections using imaging mass spectrometry, two metabolites, i.e., L-acetylcarnitine and phosphatidylcholine were increased not only preceding the peak of RGC death in the whole retina but also at the RGC layer (2.3-fold and 1.2-fold, respectively). These phospholipids propose novel mechanisms of RGC death and may serve as early biomarkers of axonal injury. The combinatory metabolomics analyses promise to illuminate pathomechanisms, reveal biomarkers, and allow the discovery of new therapeutic targets of glaucoma.

Original languageEnglish
Article number11930
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Metabolomic changes in the mouse retina after optic nerve injury'. Together they form a unique fingerprint.

Cite this