Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes

Mehdi Mirzaei, Veer B. Gupta, Joel M. Chick, Todd M. Greco, Yunqi Wu, Nitin Chitranshi, Roshana Vander Wall, Eugene Hone, Liting Deng, Yogita Dheer, Mojdeh Abbasi, Mahdie Rezaeian, Nady Braidy, Yuyi You, Ghasem Hosseini Salekdeh, Paul A. Haynes, Mark P. Molloy, Ralph Martins, Ileana M. Cristea, Steven P. Gygi & 2 others Stuart L. Graham, Vivek K. Gupta

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal tissue and vitreous humour fluid collected from glaucoma patients and age-matched controls followed by functional pathway and protein network interaction analysis. About 5000 proteins were quantified from retinal tissue and vitreous fluid of glaucoma and control eyes. Of the differentially regulated proteins, 122 were found linked with pathophysiology of Alzheimer's disease (AD). Pathway analyses of differentially regulated proteins indicate defects in mitochondrial oxidative phosphorylation machinery. The classical complement pathway associated proteins were activated in the glaucoma samples suggesting an innate inflammatory response. The majority of common differentially regulated proteins in both tissues were members of functional protein networks associated brain changes in AD and other chronic degenerative conditions. Identification of previously reported and novel pathways in glaucoma that overlap with other CNS neurodegenerative disorders promises to provide renewed understanding of the aetiology and pathogenesis of age related neurodegenerative diseases.

LanguageEnglish
Article number12685
Pages1-16
Number of pages16
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 4 Oct 2017

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Proteome
Neurodegenerative Diseases
Glaucoma
Proteins
Vitreous Body
Alzheimer Disease
Classical Complement Pathway
Protein Interaction Maps
Oxidative Phosphorylation
Proteomics
Retina
Chronic Disease
Central Nervous System
Brain

Bibliographical note

Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Cite this

Mirzaei, Mehdi ; Gupta, Veer B. ; Chick, Joel M. ; Greco, Todd M. ; Wu, Yunqi ; Chitranshi, Nitin ; Wall, Roshana Vander ; Hone, Eugene ; Deng, Liting ; Dheer, Yogita ; Abbasi, Mojdeh ; Rezaeian, Mahdie ; Braidy, Nady ; You, Yuyi ; Salekdeh, Ghasem Hosseini ; Haynes, Paul A. ; Molloy, Mark P. ; Martins, Ralph ; Cristea, Ileana M. ; Gygi, Steven P. ; Graham, Stuart L. ; Gupta, Vivek K. / Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes. In: Scientific Reports. 2017 ; Vol. 7, No. 1. pp. 1-16.
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abstract = "Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal tissue and vitreous humour fluid collected from glaucoma patients and age-matched controls followed by functional pathway and protein network interaction analysis. About 5000 proteins were quantified from retinal tissue and vitreous fluid of glaucoma and control eyes. Of the differentially regulated proteins, 122 were found linked with pathophysiology of Alzheimer's disease (AD). Pathway analyses of differentially regulated proteins indicate defects in mitochondrial oxidative phosphorylation machinery. The classical complement pathway associated proteins were activated in the glaucoma samples suggesting an innate inflammatory response. The majority of common differentially regulated proteins in both tissues were members of functional protein networks associated brain changes in AD and other chronic degenerative conditions. Identification of previously reported and novel pathways in glaucoma that overlap with other CNS neurodegenerative disorders promises to provide renewed understanding of the aetiology and pathogenesis of age related neurodegenerative diseases.",
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Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes. / Mirzaei, Mehdi; Gupta, Veer B.; Chick, Joel M.; Greco, Todd M.; Wu, Yunqi; Chitranshi, Nitin; Wall, Roshana Vander; Hone, Eugene; Deng, Liting; Dheer, Yogita; Abbasi, Mojdeh; Rezaeian, Mahdie; Braidy, Nady; You, Yuyi; Salekdeh, Ghasem Hosseini; Haynes, Paul A.; Molloy, Mark P.; Martins, Ralph; Cristea, Ileana M.; Gygi, Steven P.; Graham, Stuart L.; Gupta, Vivek K.

In: Scientific Reports, Vol. 7, No. 1, 12685, 04.10.2017, p. 1-16.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Mirzaei, Mehdi

AU - Gupta, Veer B.

AU - Chick, Joel M.

AU - Greco, Todd M.

AU - Wu, Yunqi

AU - Chitranshi, Nitin

AU - Wall, Roshana Vander

AU - Hone, Eugene

AU - Deng, Liting

AU - Dheer, Yogita

AU - Abbasi, Mojdeh

AU - Rezaeian, Mahdie

AU - Braidy, Nady

AU - You, Yuyi

AU - Salekdeh, Ghasem Hosseini

AU - Haynes, Paul A.

AU - Molloy, Mark P.

AU - Martins, Ralph

AU - Cristea, Ileana M.

AU - Gygi, Steven P.

AU - Graham, Stuart L.

AU - Gupta, Vivek K.

N1 - Copyright the Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2017/10/4

Y1 - 2017/10/4

N2 - Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal tissue and vitreous humour fluid collected from glaucoma patients and age-matched controls followed by functional pathway and protein network interaction analysis. About 5000 proteins were quantified from retinal tissue and vitreous fluid of glaucoma and control eyes. Of the differentially regulated proteins, 122 were found linked with pathophysiology of Alzheimer's disease (AD). Pathway analyses of differentially regulated proteins indicate defects in mitochondrial oxidative phosphorylation machinery. The classical complement pathway associated proteins were activated in the glaucoma samples suggesting an innate inflammatory response. The majority of common differentially regulated proteins in both tissues were members of functional protein networks associated brain changes in AD and other chronic degenerative conditions. Identification of previously reported and novel pathways in glaucoma that overlap with other CNS neurodegenerative disorders promises to provide renewed understanding of the aetiology and pathogenesis of age related neurodegenerative diseases.

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