TY - JOUR

T1 - Metabolomics of the human aqueous humor

AU - Snytnikova, Olga A.

AU - Khlichkina, Anastasiya A.

AU - Yanshole, Lyudmila V.

AU - Yanshole, Vadim V.

AU - Iskakov, Igor A.

AU - Egorova, Elena V.

AU - Stepakov, Denis A.

AU - Novoselov, Vladimir P.

AU - Tsentalovich, Yuri P.

N1 - Publisher Copyright: © 2016, Springer Science+Business Media New York.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Introduction: The optical elements of the eye—cornea, lens, and vitreous humor—are avascular tissues, and their nutrition and waste removal are provided by aqueous humor (AH). The AH production occurs through the active secretion and the passive diffusion/ultrafiltration of blood plasma. The comparison of the metabolomic profiles of AH and plasma is important for understanding of the mechanisms of biochemical processes and metabolite transport taking place in vivo in ocular tissues. Objectives: The work is aimed at the determination of concentrations of a wide range of most abundant metabolites in the human AH, the comparison of the metabolomic profiles of AH and serum, and the analysis of the post-mortem metabolomic changes in these two biological fluids. 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 blood serum and AH from living patients and human cadavers have been measured. It has been found that the level of ascorbate in AH is by two orders of magnitude higher than that in serum; the levels of other metabolites are either similar to that in serum, or differ from that by a factor of 2–5. The post-mortem metabolomic composition of both serum and AH undergoes rapid and strong changes. Conclusion: The differences between the metabolomic profiles of AH and serum for majority of metabolites can be attributed to the metabolic activity of the ocular tissues leading to the lack or excess of some metabolites, while the high concentration of ascorbate in AH demonstrates the activity of ascorbate-specific pumps at the blood-aqueous border. The post-mortem metabolomic changes are caused by the disruption of the major biochemical cycles and cell lysis. These changes should be taken into account in the analysis of disease-induced changes in post-mortem samples of the ocular tissues.

AB - Introduction: The optical elements of the eye—cornea, lens, and vitreous humor—are avascular tissues, and their nutrition and waste removal are provided by aqueous humor (AH). The AH production occurs through the active secretion and the passive diffusion/ultrafiltration of blood plasma. The comparison of the metabolomic profiles of AH and plasma is important for understanding of the mechanisms of biochemical processes and metabolite transport taking place in vivo in ocular tissues. Objectives: The work is aimed at the determination of concentrations of a wide range of most abundant metabolites in the human AH, the comparison of the metabolomic profiles of AH and serum, and the analysis of the post-mortem metabolomic changes in these two biological fluids. 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 blood serum and AH from living patients and human cadavers have been measured. It has been found that the level of ascorbate in AH is by two orders of magnitude higher than that in serum; the levels of other metabolites are either similar to that in serum, or differ from that by a factor of 2–5. The post-mortem metabolomic composition of both serum and AH undergoes rapid and strong changes. Conclusion: The differences between the metabolomic profiles of AH and serum for majority of metabolites can be attributed to the metabolic activity of the ocular tissues leading to the lack or excess of some metabolites, while the high concentration of ascorbate in AH demonstrates the activity of ascorbate-specific pumps at the blood-aqueous border. The post-mortem metabolomic changes are caused by the disruption of the major biochemical cycles and cell lysis. These changes should be taken into account in the analysis of disease-induced changes in post-mortem samples of the ocular tissues.

KW - Aqueous humor

KW - Human metabolomics

KW - Serum

KW - RESOLUTION H-1-NMR SPECTROSCOPY

KW - RAT

KW - NMR-SPECTROSCOPY

KW - ASCORBIC-ACID

KW - POSTMORTEM INTERVAL

KW - VITREOUS HUMORS

KW - AMINO-ACIDS

KW - RABBIT

KW - LENS

KW - BLOOD

UR - http://www.scopus.com/inward/record.url?scp=85000785104&partnerID=8YFLogxK

U2 - 10.1007/s11306-016-1144-0

DO - 10.1007/s11306-016-1144-0

M3 - Article

AN - SCOPUS:85000785104

VL - 13

JO - Metabolomics

JF - Metabolomics

SN - 1573-3882

IS - 1

M1 - 5

ER -