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PXD063075-1

PXD063075 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHuman Retinal Organoid Model of Disease-Relevant Photoreceptor Cell Death Amenable to Drug Screening
DescriptionDry age-related macular degeneration (AMD) is characterized by the progressive loss of retinal pigment epithelium cells in the macula, leading to photoreceptor degeneration and loss of central vision. Current treatments can only slow disease progression in some cases, but once photoreceptors are damaged, vision loss becomes irreversible. Therefore, there is an urgent need to develop therapies that prevent photoreceptor cell death. A critical step toward this goal is establishing pathophysiologically relevant human disease models for therapeutic testing. In this study, we developed a human- induced pluripotent stem cell-derived retinal organoid (RO) model that recapitulates key aspects of AMD-associated photoreceptor degeneration. Since cigarette smoking is a major environmental risk factor for AMD, we exposed ROs to cigarette smoke extract (CSE) to induce cellular stress. CSE treatment resulted in increased reactive oxygen species, mitochondrial membrane depolarization, and cell death primarily in the outer nuclear layer. Photoreceptor degeneration in this model involves the activation of the intrinsic apoptotic pathway and ferroptosis, which is accompanied by lipid peroxidation and dysregulation of the glutathione system. Comprehensive proteomic analysis confirmed the dysregulation of metabolic and stress response pathways. The integration of this model with robust, quantitative outcome measures in live ROs offers a powerful platform for preclinical drug screening and therapeutic evaluation.
HostingRepositoryPRIDE
AnnounceDate2026-04-14
AnnouncementXMLSubmission_2026-04-14_06:22:09.548.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAnthony Saviola
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-04-17 10:34:47ID requested
12026-04-14 06:22:10announced
Publication List
10.1038/S41419-026-08724-Y;
Keyword List
submitter keyword: None
Contact List
Natalia Vergara
contact affiliationUniversity of Colorado Anschutz Medical Campus
contact emailNATALIA.VERGARA@CUANSCHUTZ.EDU
lab head
Anthony Saviola
contact affiliationUniversity of Colorado Anschutz Medical Campus
contact emailanthony.saviola@cuanschutz.edu
dataset submitter
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Dataset FTP location
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