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

*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 languageEnglish
Article number12685
Pages (from-to)1-16
Number of pages16
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 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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