TY - JOUR

T1 - Quantitative metabolomic analysis of the human cornea and aqueous humor

AU - Snytnikova, Olga A.

AU - Yanshole, Lyudmila V.

AU - Iskakov, Igor A.

AU - Yanshole, Vadim V.

AU - Chernykh, Valery V.

AU - Stepakov, Denis A.

AU - Novoselov, Vladimir P.

AU - Tsentalovich, Yuri P.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Introduction: Cornea is the outermost part of the eye supplied mostly by aqueous humor (AH). Therefore, the comparison of the metabolomic compositions of AH and cornea may help to determine which compounds are produced inside the cornea, and which penetrate into cornea from AH for intra-corneal consumption. Keratoconus (KC) is the most common form of the cornea dystrophy, and the analysis of KC corneas can unravel the metabolomic changes occurring in AH and cornea of KC patients. Objectives: The work is aimed at the determination of concentrations of a wide range of metabolites in the human cornea and AH, the comparison of the metabolomic profiles of cornea and AH, and the comparison of the metabolomic compositions of samples taken from KC patients and normal donors (post-mortem). Methods: The quantitative metabolomic profiling was carried out with the use of two independent methods—high-frequency 1H NMR spectroscopy and HPLC with high-resolution ESI-MS detection. Results: The concentrations of 71 most abundant metabolites in cornea and AH from keratoconus patients and from human cadavers have been measured. It is found that the concentrations of purines and organic acids in cornea are significantly higher than in AH. The KC corneas are characterized by the enhanced levels of acetate and citrate, and also by low values of GSH/GSSG ratios. Conclusion: A significant difference in the metabolomic compositions of the human AH and cornea has been revealed. The concentrations of glucose and some amino acids in cornea are significantly lower than in AH, indicating their fast consumption inside the cornea. The high levels of organic acids, purines and GSH in cornea should be attributed to their production in the cornea. The enhanced levels of acetate and citrate as well as the low values of GSH/GSSG ratios in KC corneas are the indicators of the oxidative stress.

AB - Introduction: Cornea is the outermost part of the eye supplied mostly by aqueous humor (AH). Therefore, the comparison of the metabolomic compositions of AH and cornea may help to determine which compounds are produced inside the cornea, and which penetrate into cornea from AH for intra-corneal consumption. Keratoconus (KC) is the most common form of the cornea dystrophy, and the analysis of KC corneas can unravel the metabolomic changes occurring in AH and cornea of KC patients. Objectives: The work is aimed at the determination of concentrations of a wide range of metabolites in the human cornea and AH, the comparison of the metabolomic profiles of cornea and AH, and the comparison of the metabolomic compositions of samples taken from KC patients and normal donors (post-mortem). Methods: The quantitative metabolomic profiling was carried out with the use of two independent methods—high-frequency 1H NMR spectroscopy and HPLC with high-resolution ESI-MS detection. Results: The concentrations of 71 most abundant metabolites in cornea and AH from keratoconus patients and from human cadavers have been measured. It is found that the concentrations of purines and organic acids in cornea are significantly higher than in AH. The KC corneas are characterized by the enhanced levels of acetate and citrate, and also by low values of GSH/GSSG ratios. Conclusion: A significant difference in the metabolomic compositions of the human AH and cornea has been revealed. The concentrations of glucose and some amino acids in cornea are significantly lower than in AH, indicating their fast consumption inside the cornea. The high levels of organic acids, purines and GSH in cornea should be attributed to their production in the cornea. The enhanced levels of acetate and citrate as well as the low values of GSH/GSSG ratios in KC corneas are the indicators of the oxidative stress.

KW - Aqueous humor

KW - Cornea

KW - Human metabolomics

KW - Keratoconus

KW - LC-MS

KW - NMR

KW - OXIDATIVE STRESS

KW - METABOLITES

KW - NMR-SPECTROSCOPY

KW - POSTMORTEM INTERVAL

KW - MASS-SPECTROMETRY

KW - KERATOCONUS

KW - PATHOGENESIS

KW - DISEASES

KW - CATARACT

KW - AGE

UR - http://www.scopus.com/inward/record.url?scp=85032579536&partnerID=8YFLogxK

U2 - 10.1007/s11306-017-1281-0

DO - 10.1007/s11306-017-1281-0

M3 - Article

AN - SCOPUS:85032579536

VL - 13

JO - Metabolomics

JF - Metabolomics

SN - 1573-3882

IS - 12

M1 - 152

ER -