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; Stuart L. Graham; Vivek K. Gupta

doi:10.1038/s41598-017-12858-7

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. GygiStuart L. Graham, Vivek K. Gupta

^*Corresponding author for this work

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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.

Original language	English
Article number	12685
Pages (from-to)	1-16
Number of pages	16
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-12858-7
Publication status	Published - 4 Oct 2017

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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.

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Mirzaei, M., Gupta, V. B., Chick, J. M., Greco, T. M., Wu, Y., Chitranshi, N., Wall, R. V., Hone, E., Deng, L., Dheer, Y., Abbasi, M., Rezaeian, M., Braidy, N., You, Y., Salekdeh, G. H., Haynes, P. A., Molloy, M. P., Martins, R., Cristea, I. M., ... Gupta, V. K. (2017). Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes. Scientific Reports, 7(1), 1-16. Article 12685. https://doi.org/10.1038/s41598-017-12858-7

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

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.",

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

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.",

year = "2017",

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day = "4",

doi = "10.1038/s41598-017-12858-7",

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Mirzaei, M, Gupta, VB, Chick, JM, Greco, TM, Wu, Y , Chitranshi, N, Wall, RV, Hone, E, Deng, L, Dheer, Y, Abbasi, M, Rezaeian, M, Braidy, N, You, Y , Salekdeh, GH , Haynes, PA , Molloy, MP , Martins, R, Cristea, IM, Gygi, SP, Graham, SL & Gupta, VK 2017, 'Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes', Scientific Reports, vol. 7, no. 1, 12685, pp. 1-16. https://doi.org/10.1038/s41598-017-12858-7

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T1 - Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes

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.

AB - 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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SN - 2045-2322

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JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 12685

ER -

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

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