{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/checksum.txt"],"Xml":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/combined.prot.xml"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_C1_S6-A7_1_5684.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_A1_S6-A1_1_5676.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_A2_S6-A2_1_5677.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_B1_S6-A4_1_5680.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_A3_S6-A3_1_5678.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_B2_S6-A5_1_5681.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_C2_S6-A8_1_5685.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_C3_S6-A9_1_5686.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD063075/SParween_ttf2_B3_S6-A6_1_5682.d.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["NATALIA.VERGARA@CUANSCHUTZ.EDU"],"submitter":["Anthony Saviola"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics"],"software":[""],"submitter_keywords":[""],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD063075"],"tissue":["Cell Culture"],"sample_protocol":["Samples were reduced, alkylated, and digested using S-TrapTM micro filters (Protifi, Huntington, NY) according to the manufacturer’s protocol. Digested peptides were cleaned using PierceTM C18 Spin Tips (Thermo Scientific) according to the manufacturer's protocol, dried in a vacuum centrifuge, and resuspended in 0.1% FA in mass spectrometry-grade water. Digested peptides were loaded onto individual Evotips following the manufacturer’s protocol and separated on an Evosep One chromatography system (Evosep, Odense, Denmark) using a Pepsep column, (150 μm inner diameter, 15 cm) packed with ReproSil C18 1.9 μm, 120A resin. The system was coupled to the timsTOF Pro mass spectrometer (Bruker Daltonics, Bremen, Germany) via the nano-electrospray ion source (Captive Spray, Bruker Daltonics). The mass spectrometer was operated in PASEF mode. The ramp time was set to 100 ms and 10 PASEF MS/MS scans per topN acquisition cycle were acquired. MS and MS/MS spectra were recorded from m/z 100 to 1700. The ion mobility was scanned from 0.7 to 1.50 Vs/cm2. Precursors for data-dependent acquisition were isolated within ± 1 Th and fragmented with an ion mobility-dependent collision energy, which was linearly increased from 20 to 59 eV in positive mode. Low-abundance precursor ions with an intensity above a threshold of 500 counts but below a target value of 20000 counts were repeatedly scheduled and otherwise dynamically excluded for 0.4 min."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["Fragmentation spectra were searched against the UniProt human proteome database using the MSFragger-based FragPipe computational platform. Contaminants and reverse decoys were added to the database automatically. The precursor-ion mass tolerance and fragment-ion mass tolerance were set to 15 and 20 ppm, respectively. Fixed modifications were set as carbamidomethyl (C), and variable modifications were set as oxidation (M), two missed tryptic cleavages were allowed, and the protein-level false discovery rate (FDR) was ≤ 1%."],"omics_type":["Proteomics"],"labhead":["Natalia Vergara"],"instrument_platform":[""],"labhead_affiliation":["University of Colorado Anschutz Medical Campus"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"submitter_mail":["anthony.saviola@cuanschutz.edu"],"publication":["10.1038/S41419-026-08724-Y"],"submitter_affiliation":["University of Colorado Anschutz Medical Campus"],"submitter_country":["United States"],"additional_accession":[]},"is_claimable":false,"name":"Human Retinal Organoid Model of Disease-Relevant Photoreceptor Cell Death Amenable to Drug Screening","description":"Dry 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.","dates":{"publication":"2026-04-14","submission":"2025-04-17"},"accession":"PXD063075","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:260201","NEWT:35554","NCBITaxon:12939","NEWT:377960","NEWT:32046","NEWT:544496","NEWT:59529","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:10245","NEWT:55153","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:351581","NEWT:43186","NEWT:428146","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:1147161","NEWT:661410","NEWT:638632","NEWT:43150","NEWT:263737","NEWT:224326","NEWT:1333499","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:5702","NEWT:95648","NEWT:1589","NEWT:135622","NEWT:1349","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:383379","NEWT:1401257","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:44491","NEWT:641809","NEWT:27933","NEWT:556484","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:7719","NEWT:7959","NEWT:2261","NEWT:868565","NEWT:135674","NEWT:94323","NEWT:31156","NEWT:3112","NEWT:79329","NEWT:4442","NEWT:192875","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:284218","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:1316931","NEWT:224308","NEWT:3347","NEWT:511145","NEWT:160621","NEWT:212790","NEWT:931281","NEWT:4432","NEWT:5762","NEWT:5763","NEWT:658457","NEWT:1310161","NEWT:35525","NEWT:77133","NEWT:295358","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:2246","NEWT:2652724","NEWT:5757","NEWT:68415","NCBITaxon:4563","NEWT:5755","NEWT:44688","NEWT:44689","NEWT:44447","NEWT:752555","NEWT:498211","NEWT:5759","NEWT:347256","NEWT:1736231","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:1392","NEWT:498217","NEWT:498216","NEWT:2242","NEWT:11320","NEWT:286","NEWT:391619","NEWT:246196","NEWT:287","NEWT:246197","NEWT:145458","NEWT:633149","NEWT:1149786","NEWT:10239","NEWT:68895","NEWT:44685","NEWT:161934","NEWT:4897","NEWT:1148","NEWT:5744","NEWT:72901","NEWT:213863","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:55571","NEWT:35500","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:4896","NEWT:1262161","NEWT:1314781","NEWT:1287689","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:294","NEWT:1773","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:3711","NEWT:935293","NEWT:375146","NEWT:2065263","NEWT:177437","NEWT:1772","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:11988","NEWT:284812","NEWT:8175","NEWT:400667","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:3702","NEWT:1245466","NEWT:244366","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:586722","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:274","NEWT:7070","NCBITaxon:287","NEWT:408172","NEWT:408170","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1436733","NEWT:460519","NEWT:1247411","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:9238","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1303443","NEWT:333760","NEWT:485","NEWT:34607","NEWT:56636","NEWT:1513458","NEWT:1233681","NCBITaxon:40559","NEWT:506599","NEWT:2853422","NEWT:81077","NEWT:84588","NEWT:1279007","NEWT:1679718","NEWT:480","NEWT:65349","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:300852","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:508771","NEWT:1121405","NEWT:1883446","NEWT:253","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:93062","NEWT:34613","NCBITaxon:4932","NEWT:1748","NEWT:109760","NEWT:29031","NEWT:108673","NEWT:943274","NEWT:644223","NEWT:1263082","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:272623","NEWT:272624","NEWT:320637","NEWT:886559","NEWT:3750","NEWT:55521","NEWT:983964","NEWT:118499","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:1130798","NEWT:55529","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:1116234","NEWT:561007","NEWT:1255228","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:3983","NEWT:203696","NEWT:472","NEWT:352472","NEWT:529507","NEWT:97441","NEWT:1154756","NEWT:1071661","NEWT:1202531","NEWT:1202532","NEWT:360094","NEWT:1408223","NEWT:470","NEWT:1408224","NEWT:41364","NEWT:5911","NEWT:1313","NEWT:1218097","NEWT:1080348","NCBITaxon:50557","NEWT:1314","NEWT:39251","NEWT:39491","NEWT:212142","NCBITaxon:5811","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:1499105","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:571256","NEWT:40483","NEWT:63366","NEWT:63367","NEWT:688333","NEWT:215402","NCBITaxon:548681","NEWT:318586","NCBITaxon:5820","NEWT:1547","NEWT:272634","NEWT:198107","NEWT:1979401","NEWT:9031","NEWT: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