Metabolomics of the rat lens: A combined LC-MS and NMR study

Yanshole, Vadim V.; Snytnikova, Olga A.; Kiryutin, Alexey S.; Yanshole, Lyudmila V.; Sagdeev, R. Z.; Tsentalovich, Yuri P.

doi:10.1016/j.exer.2014.05.016

Cited by 53 publications

(54 citation statements)

References 32 publications

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“…Separation was performed on the analytical column Agilent Zorbax XDB-C18 (4.6 9 150 mm, 80 A, 5 lm) using the parameters described in the previous work (Yanshole et al 2014). The flow rate was 200 lL/min, and sample injection volume 80 lL.…”

Section: Liquid Chromatography With Mass Spectrometrymentioning

confidence: 99%

“…Mass spectra were recorded in positive-ion mode in the 50-700 m/z range at the 2 Hz sampling rate. The instrument parameters for positive ion mode and instrument calibration were taken from the work of Yanshole et al (2014). Every mass spectrometric measurement contained the time segment with the mass spectrometer calibration data, which were used for postrecalibration of the sample data if necessary.…”

Section: Liquid Chromatography With Mass Spectrometrymentioning

confidence: 99%

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Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease

et al. 2014

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Melatonin synthesis is disordered in patients with Alzheimer's disease (AD). To determine the role of melatonin in the pathogenesis of AD, suitable animal models are needed. The OXYS rats are an experimental model of accelerated senescence that has also been proposed as a spontaneous rat model of AD-like pathology. In the present study, we demonstrate that disturbances in melatonin secretion occur in OXYS rats at 4 months of age. These disturbances occur simultaneously with manifestation of behavioral abnormalities against the background of neurodegeneration and alterations in hormonal status but before the signs of amyloid-β accumulation. We examined whether oral administration of melatonin could normalize the melatonin secretion and have beneficial effects on OXYS rats before progression to AD-like pathology. The results showed that melatonin treatment restored melatonin secretion in the pineal gland of OXYS rats as well as the serum levels of growth hormone and IGF-1, the level of BDNF in the hippocampus and the healthy state of hippocampal neurons. Additionally, melatonin treatment of OXYS rats prevented an increase in anxiety and the decline of locomotor activity, of exploratory activity, and of reference memory. Thus, melatonin may be involved in AD progression, whereas oral administration of melatonin could be a prophylactic strategy to prevent or slow down the progression of some features of AD pathology.

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Section: Liquid Chromatography With Mass Spectrometrymentioning

confidence: 99%

Section: Liquid Chromatography With Mass Spectrometrymentioning

confidence: 99%

Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease

et al. 2014

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“…1), several of which are discussed in detail in later sections, and for which the following studies are representative (Chauhan et al, 2002b; Hammond et al, 2001; Hawse et al, 2003; Lachke et al, 2012b; Lampi et al, 2002; Sousounis et al, 2013; Tsentalovich et al, 2015; Ueda et al, 2002; Yanshole et al, 2014). These approaches have generated immense quantities of data.…”

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confidence: 99%

Systems biology of lens development: A paradigm for disease gene discovery in the eye

Anand

Lachke

2017

Experimental Eye Research

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Over the past several decades, the biology of the developing lens has been investigated using molecular genetics-based approaches in various vertebrate model systems. These efforts, involving target gene knockouts or knockdowns, have led to major advances in our understanding of lens morphogenesis and the pathological basis of cataracts, as well as of other lens related eye defects. In particular, we now have a functional understanding of regulators such as Pax6, Six3, Sox2, Oct1 (Pou2f1), Meis1, Pnox1, Zeb2 (Sip1), Mab21l1, Foxe3, Tfap2a (Ap2-alpha), Pitx3, Sox11, Prox1, Sox1, c-Maf, Mafg, Mafk, Hsf4, Fgfrs, Bmp7, and Tdrd7 in this tissue. However, whether these individual regulators interact or their targets overlap, and the significance of such interactions during lens morphogenesis, is not well defined. The arrival of high-throughput approaches for gene expression profiling (microarrays, RNA-sequencing (RNA-seq), etc.), which can be coupled with chromatin immunoprecipitation (ChIP) or RNA immunoprecipitation (RIP) assays, along with improved computational resources and publically available datasets (e.g. those containing comprehensive protein-protein, protein-DNA information), presents new opportunities to advance our understanding of the lens tissue on a global systems level. Such systems-level knowledge will lead to the derivation of the underlying lens gene regulatory network (GRN), defined as a circuit map of the regulator-target interactions functional in lens development, which can be applied to expedite cataract gene discovery. In this review, we cover the various systems-level approaches such as microarrays, RNA-seq, and ChIP that are already being applied to lens studies and discuss strategies for assembling and interpreting these vast amounts of high-throughput information for effective dispersion to the scientific community. In particular, we discuss strategies for effective interpretation of this new information in the context of the rich knowledge obtained through the application of traditional single-gene focused experiments on the lens. Finally, we discuss our vision for integrating these diverse high-throughput datasets in a single web-based user-friendly tool iSyTE (integrated Systems Tool for Eye gene discovery) – a resource that is already proving effective in the identification and characterization of genes linked to lens development and cataract. We anticipate that application of a similar approach to other ocular tissues such as the retina and the cornea, and even other organ systems, will significantly impact disease gene discovery.

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“…Twenty-one, male, Sprague Dawley rats were included in the post-mortem study (42 eyes in total) and six rats were included in the tissue comparison study; all rats were in the age-range of [7][8][9][10][11][12] weeks. The rats were kept in the same room under standard laboratory conditions and fed with standard chow.…”

Section: Animalsmentioning

confidence: 99%

“…It has been used to characterise normal ocular tissues and biofluids including the tear film, lens, vitreous and retina. [6][7][8][9][10] It has also been used to study ageing, a variety of ocular pathologies, metabolite transport in the retina, effects of drugs and metabolic changes during corneal organ culture for transplantation. [11][12][13][14][15] Aqueous and vitreous are the most accessible intraocular samples that can be obtained in clinical studies, and these have been used to interrogate the metabolic activities of surrounding ocular structures.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina

Tan

Mullard

Hollywood

et al. 2016

Experimental Eye Research

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and 48 hours post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 o C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 hours post-mortem when eyes were stored at 4 o C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 hours post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 hours. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were exclusively found in the retina and not other tissues. In conclusion, mass

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Metabolomics of the rat lens: A combined LC-MS and NMR study

Cited by 53 publications

References 32 publications

Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease

Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease

Systems biology of lens development: A paradigm for disease gene discovery in the eye

Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina

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