Low expression of GSTP1 in the aqueous humour of patients with primary open‐angle glaucoma

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Abstract

Primary open‐angle glaucoma (POAG) is characterized by irreversible neurodegeneration accompanied by visual field defects and high intraocular pressure. Currently, an effective treatment is not available to prevent the progression of POAG, other than treatments to decrease the high intraocular pressure. We performed proteomic analysis of aqueous humour (AH) samples from patients with POAG combined with cataract and patients with cataract to obtain a better understanding of the pathogenesis of POAG and explore potential treatment targets for this condition. Samples were collected from 10 patients with POAG combined with cataract and 10 patients with cataract. Samples from each group were pooled. A high‐resolution, label‐free, liquid chromatography‐tandem mass spectrometry‐based quantitative proteomic analysis was performed. In total, 610 proteins were identified in human AH samples from the two groups. A total of 48 up‐regulated proteins and 49 down‐regulated proteins were identified in the POAG combined with cataract group compared with the control group. Gene Ontology (GO) analysis revealed key roles for these proteins in inflammation, immune responses, growth and development, cellular movement and vesicle‐mediated transport in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the down‐regulated expression of glutathione S‐transferase P (GSTP1) in the glutathione metabolism signalling pathway in the POAG combined with cataract group. Additionally, certain significantly differentially expressed proteins in the proteomic profile were verified by enzyme‐linked immunosorbent assay (ELISA). GSTP1 levels were reduced in the human AH samples from the POAG combined with cataract group, based on the results of ELISA and proteomic profiling. Therefore, GSTP1, a redox‐related marker, may be involved in the pathological process of POAG and may become a treatment target in the future.

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Most cited references 55

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MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.

Jürgen Cox, Matthias Mann (2008)

Efficient analysis of very large amounts of raw data for peptide identification and protein quantification is a principal challenge in mass spectrometry (MS)-based proteomics. Here we describe MaxQuant, an integrated suite of algorithms specifically developed for high-resolution, quantitative MS data. Using correlation analysis and graph theory, MaxQuant detects peaks, isotope clusters and stable amino acid isotope-labeled (SILAC) peptide pairs as three-dimensional objects in m/z, elution time and signal intensity space. By integrating multiple mass measurements and correcting for linear and nonlinear mass offsets, we achieve mass accuracy in the p.p.b. range, a sixfold increase over standard techniques. We increase the proportion of identified fragmentation spectra to 73% for SILAC peptide pairs via unambiguous assignment of isotope and missed-cleavage state and individual mass precision. MaxQuant automatically quantifies several hundred thousand peptides per SILAC-proteome experiment and allows statistically robust identification and quantification of >4,000 proteins in mammalian cell lysates.

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The pathophysiology and treatment of glaucoma: a review.

Robert N. Weinreb, Tin Aung, Felipe Medeiros (2014)

Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.

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Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma.

Janice A. Vranka, Mary Kelley, Ted Acott … (2015)

The trabecular meshwork (TM) is located in the anterior segment of the eye and is responsible for regulating the outflow of aqueous humor. Increased resistance to aqueous outflow causes intraocular pressure to increase, which is the primary risk factor for glaucoma. TM cells reside on a series of fenestrated beams and sheets through which the aqueous humor flows to exit the anterior chamber via Schlemm's canal. The outer trabecular cells are phagocytic and are thought to function as a pre-filter. However, most of the outflow resistance is thought to be from the extracellular matrix (ECM) of the juxtacanalicular region, the deepest portion of the TM, and from the inner wall basement membrane of Schlemm's canal. It is becoming increasingly evident that the extracellular milieu is important in maintaining the integrity of the TM. In glaucoma, not only have ultrastructural changes been observed in the ECM of the TM, and a significant number of mutations in ECM genes been noted, but the stiffness of glaucomatous TM appears to be greater than that of normal tissue. Additionally, TGFβ2 has been found to be elevated in the aqueous humor of glaucoma patients and is assumed to be involved in ECM changes deep with the juxtacanalicular region of the TM. This review summarizes the current literature on trabecular ECM as well as the development and function of the TM. Animal models and organ culture models targeting specific ECM molecules to investigate the mechanisms of glaucoma are described. Finally, the growing number of mutations that have been identified in ECM genes and genes that modulate ECM in humans with glaucoma are documented.

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Author and article information

Contributors

Xiaorong Li: xiaorli@163.com

Lijie Dong: aitaomubang@126.com

Journal

Journal ID (nlm-ta): J Cell Mol Med

Journal ID (iso-abbrev): J Cell Mol Med

Journal ID (doi): 10.1111/(ISSN)1582-4934

Journal ID (publisher-id): JCMM

Title: Journal of Cellular and Molecular Medicine

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1582-1838

ISSN (Electronic): 1582-4934

Publication date (Electronic): 17 February 2021

Publication date (Print): March 2021

Volume: 25

Issue: 6 ( doiID: 10.1111/jcmm.v25.6 )

Pages: 3063-3079

Affiliations

[ ¹ ] Tianjin Key Laboratory of Retinal Functions and Diseases Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science Eye Institute and School of Optometry Tianjin Medical University Eye Hospital Tianjin China

[ ² ] Ophthalmology Department of People's Hospital of Hotan District Xinjiang China

[ ³ ] Department of Physiology University of Oklahoma Health Sciences Center Oklahoma OK USA

Author notes

[*] [* ] Correspondence

Lijie Dong and Xiaorong Li, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Fukang Road 251, Tianjin, China.

Emails: aitaomubang@ 123456126.com (LD) and xiaorli@ 123456163.com (XL)

Author information

Liming Wang https://orcid.org/0000-0002-5504-1366

Yaru Hong https://orcid.org/0000-0001-9565-4979

Article

Publisher ID: JCMM16361

DOI: 10.1111/jcmm.16361

PMC ID: 7957170

PubMed ID: 33599104

SO-VID: 82a1adb7-f2c2-436a-b24e-8f8914a71bd4

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 21 October 2020

Date received : 07 February 2020

Date accepted : 21 January 2021

Page count

Figures: 6, Tables: 4, Pages: 17, Words: 9284

Funding

Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;

Award ID: 81570872

Funded by: General Project of Natural Science Foundation of Xinjiang Uygur Autonomous Region

Award ID: 2020D01A06

Funded by: Tianjin Clinical Key Discipline Project

Award ID: TJLCZDXKM012/005

Funded by: Tianjin Municipal Health Planning Commission Young Talents New Talent Project

Funded by: Tianjin Research Program of Application Foundation and Advanced Technology

Award ID: 15JCYBJC24900

Funded by: Tianjin University ‘training Program for Young and Middle‐aged backbone innovative talents’ , open-funder-registry 10.13039/501100004517;

Funded by: Young Creative Talents Project of Eye Hospital of Tianjin Medical University

Award ID: YDYYRCXM‐C2018‐01/02/03

Funded by: Young Medical Talents Program of Tianjin Health and Family Planning Commission

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source-schema-version-number 2.0

cover-date March 2021

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.9 mode:remove_FC converted:15.03.2021

ScienceOpen disciplines: Molecular medicine

Keywords: aqueous humour,cataract,gstp1,inflammation,oxidative stress,primary open‐angle glaucoma,proteome

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: aqueous humour, cataract, gstp1, inflammation, oxidative stress, primary open‐angle glaucoma, proteome

Low expression of GSTP1 in the aqueous humour of patients with primary open‐angle glaucoma

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Abstract

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Network and Systems Medicine

Most cited references 55

MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.

The pathophysiology and treatment of glaucoma: a review.

Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma.

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