PXD082362-1

PXD082362 is an original dataset announced via ProteomeXchange.

Title	VCP inhibition preserves photoreceptor integrity under hydroquinone induced oxidative stress in a human iPSC RPE porcine neuroretina co culture model
Description	Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in older adults, driven by early retinal pigment epithelium (RPE) dysfunction followed by photoreceptor degeneration. Cigarette smoke is a major environmental risk factor for AMD; hydroquinone (HQ), a redox-active smoke component, induces oxidative stress and apoptosis in RPE cells. How RPE stress propagates to photoreceptor degeneration, and how it might be therapeutically blocked, remains unclear. We used a human iPSC-RPE/porcine neuroretina explant co-culture system to model HQ-induced retinal stress and tested whether inhibiting valosin-containing protein (VCP) with ML240 protects the neuroretina. HQ induced apoptosis in iPSC-RPE and caused photoreceptor degeneration in co-cultured explants (reduced ONL rows, shortened outer segments). ML240 did not block RPE apoptosis but significantly preserved photoreceptor outer segment length and cone density under HQ stress. To investigate the molecular basis of this protection, quantitative proteomics (dia-PASEF, timsTOF Ultra 2; DIA-NN library-free search against the porcine UniProt database) was performed on porcine neuroretina explants from iPSC-RPE/explant co-cultures under three conditions DMSO vehicle, HQ, and HQ+ML240 with five biological replicates each. Combined with cytochrome c immunolocalization, the proteomic data indicate that ML240 reduces ER stress markers, increases antioxidant response proteins, and preserves cytochrome c enrichment in photoreceptor inner segments, consistent with improved mitochondrial integrity. These findings establish the iPSC-RPE/neuroretina co-culture as a platform for studying cell type-specific retinal responses to environmental stress, and identify VCP inhibition as a candidate neuroprotective strategy in oxidative stress-related retinal degeneration.
HostingRepository	MassIVE
AnnounceDate	2026-08-09
AnnouncementXML	Submission_2026-08-09_23:42:32.661.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mohamed Ali Jarboui
SpeciesList	scientific name: Sus scrofa; common name: pig; NCBI TaxID: 9823;
ModificationList	Carbamidomethyl; Acetyl; Oxidation
Instrument	timsTOF Ultra 2

Revision	Datetime	Status	ChangeLog Entry
0	2026-08-09 14:35:03	ID requested
⏵ 1	2026-08-09 23:42:33	announced

no publication

submitter keyword: DIA, Proteomics, VCP, Oxidative stress, AMD, iPSC derived RPE, Porcine Retina co-culture, DatasetType:Proteomics

Mohamed Ali Jarboui
contact affiliation	Core Facility Medical Proteomics, University Tuebingen
contact email	mohamed-ali.jarboui@uni-tuebingen.de
lab head
Mohamed Ali Jarboui
contact affiliation	University klinikum Tuebingen
contact email	mohamed-ali.jarboui@uni-tuebingen.de
dataset submitter

MassIVE dataset URI

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