NMR-Based Metabolomics of Non-Human Primate Ocular Tissues: A Dataset
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Nuclear Magnetic Resonance (NMR) -
SUBMITTER: Vadim Yanshole
PROVIDER: MTBLS8943 | MetaboLights | 2023-11-16
REPOSITORIES: MetaboLights
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| MTBLS8943 | Other | |||
| FILES | Other | |||
| a_MTBLS8943_NMR___metabolite_profiling.txt | Txt | |||
| i_Investigation.txt | Txt | |||
| m_MTBLS8943_NMR___metabolite_profiling_v2_maf.tsv | Tabular |
Items per page: 5 1 - 5 of 6 |
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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.
2017-11-06 | MTBLS386 | MetaboLights
Project description:Aqueous humor (AH) is the fluid in the anterior and posterior chambers of the eye that contains proteins regulating ocular homeostasis. Analysis of aqueous humor proteome is challenging mainly due to low sample volume and protein concentration. In this study, by utilizing state of the art technology, we performed Liquid-Chromatography Mass spectrometry (LC-MS/MS) analysis of 88 aqueous humor samples from subjects undergoing cataract surgery.
2021-09-09 | PXD022463 | Pride
Project description:<p><strong>INTRODUCTION:</strong> Metabolites are essential for the proper functioning of the eye lens, they either enter the lens from the aqueous humor (AH), or are synthesized in the lens epithelium. Antioxidants, osmolytes and UV filters are especially important for the lens protection, and their lack may cause the development of ophthalmic diseases.</p><p><strong>OBJECTIVES:</strong> Comparison of the metabolomic compositions of lenses and AH taken from cataract patients with that taken from human cadavers without cataract can shed light onto molecular mechanisms underlying onset of age-related nuclear cataract.</p><p><strong>METHODS:</strong> Combined use of 1H nuclear magnetic resonance and high performance liquid chromatography with optical and high-resolution mass spectrometric detection for the identification and quantification of metabolites in the lens and AH extracts.</p><p><strong>RESULTS:</strong> The concentrations of 86 metabolites were determined for four groups of samples, including lenses and AH from cataract patients and from human cadavers. In cataractous lens the most abundant metabolites are (in descending order): myo-inositol, lactate, acetate, glutamate, glutathione; in AH-lactate, glucose, glutamine, alanine, valine. The concentrations of the majority of metabolites in normal post-mortem samples of both lens and AH are higher than that in samples from the cataract patients.</p><p><strong>CONCLUSIONS:</strong> Comparison of metabolite concentrations in lens and corresponding AH reveal that the most important for the lens protection metabolites are synthesized in the lens epithelial cells. The reduced levels of antioxidants, UV filters, and osmolytes were found in the cataractous lenses what cannot be explained by post-mortem changes in normal lens; that indicates that the age-related nuclear cataract development may originate from the dysfunction of the lens epithelial cells.</p>
2022-11-07 | MTBLS740 | MetaboLights
Project description:The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some, including glaucoma and cataract, are among the most prevalent causes of blindness. To characterize the cell types that comprise these tissues, we generated an anterior segment cell atlas of the human eye using high throughput single-nucleus RNA sequencing (snRNAseq). We profiled 191,992 single nuclei from non-diseased anterior segment tissues from 6 human donors, identifying >60 cell types. Many are discrete, whereas others in lens and cornea form continua, corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment revealing that some cell types are unique to single structure whereas others are shared across tissues. This integrated cell atlas was then used to investigate cell type-specific expression patterns of more than >900 human ocular disease genes identified either through Mendelian inheritance patterns or genome-wide association studies (GWAS).
2022-07-11 | GSE199013 | GEO
Project description:<p><strong>INTRODUCTION:</strong> Application of metabolomic methods to forensic studies may expand the limits of the post-mortem interval (PMI) estimation, and improve the accuracy of the estimation. To this end, it is important to determine which tissue is the most suitable for analysis, and which compounds are the most promising candidates for PMI estimation.</p><p><strong>OBJECTIVES:</strong> This work is aimed at the comparison of human serum, aqueous humor (AH), and vitreous humor (VH) as per- spective tissues for metabolomic-based PMI estimation, at the determination of most promising PMI biomarkers, and at the development of method of PMI estimation based on the measurement of concentrations of PMI biomarkers.</p><p><strong>METHODS:</strong> Quantitative metabolomic pro ling of samples of the human serum, AH, and VH taken at di erent PMIs has been performed with the use of NMR spectroscopy.</p><p><strong>RESULTS:</strong> It is found that the metabolomic changes in anatomically isolated ocular uids are slower and smoother than that in blood. A good positive time correlation (Pearson coe cient r > 0.5) was observed for several metabolites, including hypox- anthine, choline, creatine, betaine, glutamate, and glycine. A model for PMI estimation based on concentrations of several metabolites in AH and VH is proposed.</p><p><strong>CONCLUSIONS:</strong> The obtained results demonstrate that the metabolomic analysis of AH and VH is more suitable for the PMI estimation than that of serum. The compounds with good positive time correlation can be considered as potential PMI biomarkers.</p><p><br></p>
2021-02-02 | MTBLS1518 | MetaboLights
Project description:To better understand the molecular changes in the aqueous humor (AH) content with glaucoma, we analyzed the microRNA (miRNA) profiles of AH samples from patients with Primary Open Angle Glaucoma (POAG) and Exfoliation Glaucoma (XFG) compared to non-glaucoma controls.
2018-02-08 | GSE105269 | GEO
Project description:Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure, which is currently the only controllable treatment approach. Elevated intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor (AH). Utilizing CRISPR Cas9 to disrupt the expression of the AQP1 protein, which decreases the ciliary AH secretion, resulted in an approximate 22% reduction in intraocular pressure. Nevertheless, the effectiveness of single-gene therapies is limited. To address this limitation, we conducted experiments using two mouse models of ocular hypertension. Our findings indicate that reducing the expression of the genes Rock1 and Rock2, which are associated with the outflow of AH at the trabecular meshwork (TM), as well as the genes Aqp1 and Adrb2, which are related to the generation of AH at the ciliary body (CB), can significantly reduce intraocular pressure and provide protection to the retina ganglion cells (RGCs), ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2, or Aqp1 and Adrb2, reduces the IOP and secures RGCs by single-cell sequencing.
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Project description:Chronic ocular pathologies such as cataracts and glaucoma are emerging as an important problem for public health due to the changes in lifestyle and longevity. These age-related ocular diseases are largely mediated by oxidative stress. Small extracellular vesicles (sEVs) are involved in cell-to-cell communication and transport. There is an increasing interest about the function of small extracellular vesicles (sEVs) in the eye. However, the proteome content and characterization of sEVs released by ocular cells under pathological conditions are not yet well known. Here, we aimed to analyze the protein profile of sEVs and intracellular protein content from two ocular cell lines (lens epithelial cells and retinal ganglion cells) exposed to oxidative stress to identify altered proteins that could serve as potential diagnostic biomarkers. The protein content was analyzed by quantitative mass spectrometry-based proteomics. Validation was performed by WB and ELISA using cell extracts and aqueous humor from cataract and glaucoma patients. After data analysis, 176 and 7 dysregulated proteins with an expression ratio≥1.5 were identified in lens epithelial cells’ protein extract and sEVs, respectively, upon oxidative stress induction. In retinal ganglion cells, oxidative stress induction resulted in the dysregulation of 1033 proteins in cell extracts and 9 proteins in sEVs. In addition, by WB and ELISA, the dysregulation of proteins was mostly confirmed in aqueous humor samples from cataract or glaucoma patients in comparison to ICL individuals, with RAD23B showing high glaucoma diagnostic ability. Importantly, this work expands the knowledge of the proteome characterization of cataracts and glaucoma and provides new potential diagnostic glaucoma biomarkers.
2024-10-04 | PXD054459 | Pride
Project description:Identification of genes involved in ocular birth defects remains a challenge. To facilitate the identification of genes associated with cataract, we developed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE contains microarray gene expression profiles of the mouse embryonic lens as it transitions from the stage of placode invagination to that of vesicle formation. We identified differentially regulated genes by comparing lens microarray profiles to those representing whole embryonic body (WB) without ocular tissue. These were then utilized to generate a ranked list of lens-genes enrichment, which can be viewed as iSyTE tracks in the UCSC Genome browser to aid identification of genes with lens function. We microdissected embryonic lens from mice at E10.5, E11.5, and E12.5 (triplicate at each time point). To have a proper control, we also generated gene expression profiles of whole embryonic body (WB) at these time points. For comparative analysis, we also generated gene expression profiles of E13.5 tooth germs tissues, and matched WB. These profiles are used to identify lens and tooth specific gene expression enrichment at these embryonic time points. This dataset is then used to prioritize analysis of candidate cataract associated genes.
2012-02-16 | E-GEOD-32334 | biostudies-arrayexpress
Project description:MicroRNA expression in the mouse eye.MicroRNAs (miRNAs) are key regulators of biological processes. To define miRNA function in the eye, it is essential to determine a high-resolution profile of their spatial and temporal distribution. In this report, we present the first comprehensive survey of miRNA expression in ocular tissues, using both microarray and RNA in situ hybridization (ISH) procedures. We initially determined the expression profiles of miRNAs in the retina, lens, cornea and retinal pigment epithelium of the adult mouse eye by microarray. Each tissue exhibited notably distinct miRNA enrichment patterns and cluster analysis identified groups of miRNAs that showed predominant expression in specific ocular tissues or combinations of them. Next, we performed RNA ISH for over 220 miRNAs, including those showing the highest expression levels by microarray, and generated a high-resolution expression atlas of miRNAs in the developing and adult wild-type mouse eye, which is accessible in the form of a publicly available web database. We found that 122 miRNAs displayed restricted expression domains in the eye at different developmental stages, with the majority of them expressed in one or more cell layers of the neural retina . This analysis revealed miRNAs with differential expression in ocular tissues and provided a detailed atlas of their tissue-specific distribution during development of the murine eye. The combination of the two approaches offers a valuable resource to decipher the contributions of specific miRNAs and miRNA clusters to the development of distinct ocular structures. microRNA profiling of ocular tissues from mouse. In particular we analysed the cornea, lens, Retina Pigment Epithelium (RPE) and retina and compared them against RNA extracted from the entire eye. The purpose of this experiment was to understand which microRNAs are present nd/or show differential expression in the various structures of the eye (cornea, lens, RPE, retina). The samples numbered 1 & 2 (i.e. CORNEA1, CORNEA2 etc ) are biological replicates, prepared from tissues dissecyed from different groups of wild-type animals. RNA extracted from the entire eye (EYE) served as the unique reference sample. For each tissue to be analysed we performed the following hybridizations: - 2 slides for lens (LENS1, LENS2) vs entire eye (EYE) - 2 slides for RPE (RPE1, RPE2) vs entire eye (EYE) - 2 slides for retina (RETINA1, RETINA2) vs entire eye (EYE) - 2 slides for cornea (CORNEA1, CORNEA2) vs entire eye (EYE) - 1 slide for entire eye (EYE) vs entire eye (EYE)
2010-11-22 | E-GEOD-22882 | biostudies-arrayexpress