Dataset Information

Quantitative metabolomic analysis of the human cornea and aqueous humor

ABSTRACT: 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.

INSTRUMENT(S): Bruker

SUBMITTER: Vadim Yanshole

PROVIDER: MTBLS444 | MetaboLights | 2018-06-20

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MTBLS444	Other
	FILES	Other
	a_MTBLS444_human_blood-ah_metabolites_metabolite_profiling_NMR_spectroscopy.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS444_human_blood-ah_metabolites_metabolite_profiling_NMR_spectroscopy_v2_maf.tsv	Tabular

Items per page:

1 - 5 of 7

Similar Datasets

Project description: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 aqueous humor (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 (LC-MS). 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.

Project description:Background & aims: The role of microRNAs (miRNAs) in Alcoholic Hepatitis (AH) and their potential as therapeutic targets in liver disease has not been explored yet. This study aims at profiling miRNA in AH and identifying dysregulated miRNAs involved in AH pathophysiology. Methods: miRNA expression arrays were performed in 13 AH, 5 alcohol liver disease-induced cirrhosis (ALD-CH), 5 nonalcoholic steatohepatitis induced cirrhosis (NASH-CH), 4 HCV-induced cirrhosis (HCV-CH) and 6 non-injured liver control samples. Genome wide expression profile was retrieved for 12 paired AH and control samples. MiRNA and mRNA expression data was integrated and identified miRNAs were validated in AH samples and in animal models of liver injury. Results: The miRNA array showed 111 upregulated and 66 downregulated miRNAs in AH versus healthy subjects. The comparison of miRNA profile in liver samples from AH among ALD-CH, HCV-CH and NASH-CH identified 18 miRNAs specifically dysregulated in AH. Integrative miRNA and mRNA analysis in AH identified dysregulated miRNAs for which their target genes were also dysregulated. A functional analysis of identified miRNAs and their targets revealed their involvement in the regulation of canonical pathways related to apoptosis, fatty acid metabolism and cell cycle among others. miRNAs expression (miR-182, miR-21, miR-155, miR-214, miR-432, miR-422a) was validated in an independent cohort of AH. MiR-182 expression correlated with cholestasis, disease severity and short-term mortality. Moreover, miR-182 expression is associated to cholestasis with ductular reaction but not to fibrosis and inflammation in animal models of liver injury. Conclusions: AH is characterized by an important dysregulation of miRNA expression with a unique miRNA profile. MiRNAs specifically expressed in AH are associated to cholestasis… Uncovered miRNAs are involved in important pathophysiological features in AH suggesting ta regulation of he role of miRNAs in the regulation of AH, and highlight miR-182 as a potential regulator of its pathophysiology.

Dataset Information

Quantitative metabolomic analysis of the human cornea and aqueous humor

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets