PXD033173-1

PXD033173 is an original dataset announced via ProteomeXchange.

Title	Investigating Autophagy Disruption Induces Neurodegeneration in Glaucoma OPTN(E50K) Retinal Ganglion Cells
Description	Retinal ganglion cells (RGCs) are the sole projection neurons that connect the eye with the brain, and the degeneration of these cells in diseases such as glaucoma results in vision loss or blindness. Similar to other neurons throughout the central nervous system, RGCs are postmitotic and therefore highly dependent upon autophagy to remove damaged proteins or organelles to maintain proper cellular homeostasis. Autophagy deficits have been implicated in multiple neurodegenerative diseases including glaucoma. In addition, a subpopulation of glaucoma patients possesses mutations in the autophagy receptor Optineurin (OPTN) resulting glaucoma within a normal range of intraocular pressure, with the OPTN(E50K) mutation known to induce a severe degeneration. Despite this, our knowledge of how autophagy impairment promotes neurodegeneration within RGCs remains limited. We advanced a human pluripotent stem cell (hPSC) model of RGC neurodegeneration with an underlying OPTN(E50K) mutation to study how autophagy disruption contributes to RGC neurodegeneration. We identified OPTN protein was reduced but accumulated within the somas in RGCs with the OPTN(E50K) mutation, and this accumulation was associated with a decrease in autophagic flux. To rule out the possibilities that the specificity of the antibody incapable to recognize E50K region resulting the reduction of OPTN protein, we performed proteomics analysis at week 2 hPSC-RGCs of post purification and identified 154 downregulated proteins as well as 178 upregulated proteins associated with OPTN(E50K) RGCs compared with isogenic controls. Taken together, we identified proteins that were altered by OPTN(E50K) mutation in RGCs, and which may provide potential mechanisms that contribute to RGC neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_08:56:24.498.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD033173
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-12 02:36:16	ID requested
⏵ 1	2025-05-06 08:56:25	announced

10.6019/PXD033173;

Huang KC, Gomes C, Shiga Y, Belforte N, VanderWall KB, Lavekar SS, Fligor CM, Harkin J, Hetzer SM, Patil SV, Di Polo A, Meyer JS, Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction. Acta Neuropathol Commun, 12(1):164(2024) [pubmed]

10.1186/s40478-024-01872-2;

submitter keyword: autophagy,Human pluripotent stem cell, retinal ganglion cells

Amber Mosley
contact affiliation	IUSM Biochemistry and Molecular Biology, Center for Proteome Analysis, Indianapolis, IN
contact email	almosley@iu.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033173
     1. Label: PRIDE project
     2. Name: Investigating Autophagy Disruption Induces Neurodegeneration in Glaucoma OPTN(E50K) Retinal Ganglion Cells