PXD033722-1

PXD033722 is an original dataset announced via ProteomeXchange.

Title	Proteome Remodeling of the Eye Lens at 50 Years Identified with Data-Independent Acquisition
Description	The eye lens is responsible for focusing and transmitting light to the retina. The lens does this in the absence of organelles yet maintains transparency for at least five decades before onset of age-related nuclear cataract (ARNC). It is hypothesized that oxidative stress contributes significantly to ARNC formation. It is additionally hypothesized that transparency is maintained by a microcirculation system (MCS) that delivers antioxidants to the lens nucleus and exports small molecule waste. Commonly used data-dependent acquisition (DDA) proteomics methods are hindered by the dynamic range of protein expression in the lens and provide limited context to age-related changes in the lens. In this study we utilized data-independent acquisition (DIA) mass spectrometry proteomics to analyze the urea insoluble, membrane protein fractions of 16 human lenses subdivided into three spatially distinct lens regions to characterize age-related changes, particularly concerning the lens MCS and oxidative stress response. In this pilot cohort, using the DIA approach, we measured 4,788 distinct protein groups, and 46,681 peptides, more than in any previous human lens DDA approach. Our results reveal age-related changes previously known in lens biology and expand on these findings, taking advantage of the rich dataset afforded by DIA mass spectrometry. Principally, we demonstrate that a significant proteome remodeling event occurs at approximately 50 years of age, resulting in metabolic preference for anaerobic glycolysis established with organelle degradation, decreased abundance of protein networks involved in calcium-dependent cell-cell contacts while retaining networks related to oxidative stress response. Further, we demonstrate the first identification of multiple antioxidant transporter proteins not previously shown in the human lens and describe their spatiotemporal and age-related abundance changes. Finally, we demonstrate that Aquaporin-5, among other proteins, is depleted with age. We suggest that the continued accumulation of each of these age-related outcomes in proteome remodeling contribute to decrease in fiber cell permeability and result in ARNC formation.
HostingRepository	MassIVE
AnnounceDate	2022-12-05
AnnouncementXML	Submission_2022-12-05_07:56:21.335.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lee Cantrell
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Deamidated
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-05 17:14:23	ID requested
⏵ 1	2022-12-05 07:56:21	announced

submitter keyword: Data-Independent Acquisition, DIA, Age, Aging, Eye, Lens

Kevin Schey
contact affiliation	Vanderbilt University
contact email	k.schey@vanderbilt.edu
lab head
Lee Cantrell
contact affiliation	Vanderbilt University
contact email	lee.s.cantrell@vanderbilt.edu
dataset submitter

MassIVE dataset URI

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