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Kindermans"],"technology_type":["Mass Spectrometry","Bottom-up proteomics","Data-independent acquisition"],"disease":["Aniridia"],"software":[""],"submitter_keywords":["Wound healing","Tear proteomics","Aniridia","Pax6"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD070553"],"tissue":["Tear"],"sample_protocol":["For proteomic analysis comparing the basal state and 18h after right eye abrasion, the samples of two right eyes on the one hand and two left eyes on the other, issued from two same sex, same genotype mice, and same condition, were collected using a fine capillary tube placed at the outer edge of the eye,  combined into a single tube, added to a volume of 12 µL Ammonium Bicarbonate (ABC) buffer. During the collection process at the animal facility, the samples were kept on ice at 4 °C and were subsequently stored at −80 °C for long-term preservation. Tear samples were thawed on ice at 4 °C, and the total protein concentration was determined using a NanoDrop One Microvolume UV–Vis Spectrophotometer (Thermo Fisher Scientific, reference ND-ONE-W) with 2 µL of each sample. 5µg of total protein are reduced, alkylated and digested with trypsin using automated SP3 protocol (figure 1) on the Bravo 96LT (Agilent Technologies). Peptides are desalted and injected in triplicate on the system Evosep one/timsTOF HT (Bruker Daltonics).  The samples were reconstituted in 10 µL of Phase A for Q-TOF analysis (2% ACN, 0.1% FA in HPLC-grade water) in polypropylene mass spectrometry vials (Agilent Technologies, reference 5190–3155). A 1 µL aliquot from each 10 µL sample was analyzed online using the NanoElute® High-Performance Liquid Chromatography (HPLC) system (Bruker) connected to the Impact II Quadrupole Time-Of-Flight (Q-TOF) mass spectrometer (Bruker). Each sample was analyzed in triplicate. Peptides were separated using a C18 column (FORTY, reference 1,842,619 from Bruker; 75 µm x 400 mm; Acclaim Pepmap RSLC, C18, 1.9 µm, 120 Å) following a gradient: 2–15% Phase B over 55 minutes, 15–25% over 25 minutes, 25–35% over 10 minutes, and 35–95% over 10 minutes (Phase A = 2% ACN, 0.1% FA in HPLC-grade water; Phase B = 0.1% FA in 90% ACN). The column was maintained at 50 °C, with a flow rate set to 300 nL/min. All reagents, including water, acetonitrile (ACN), and formic acid (FA), were HPLC grade and obtained from Biosolve (Dieuze, France)."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["Protein identification is performed with DIA-NN software (version 1.8.1). The parameters used are the following: the digestion enzyme is trypsin, the number of missed cleavages is 1, the minimum peptide size is 7 amino acids, the precursor charge range set from 1 to 4, the precursor m/z set from 300 to 1800 and a protein identification FDR was set at 1%. The Uniprot database of the mouse proteome is used as reference (Release_2024_03). Some modifications, induced by the sample preparation protocol, are studied: asparagine deamidation and methionine oxidation as variable modifications and cysteine carbamidomethylation as fixed modification. The maximum number of variable modifications set to 2.  LFQ intensities obtained were processed using the DIA-Analyst platform (version 0.8.6). For biological replicates, proteins without at least 70% of valid values for at least one group were eliminated. The LFQ data for each protein were transformed by applying the log2(x) formula and grouped according to genotype (PAX6+/- or Pax6+/+). Missing values were imputed with bpca method. A cutoff of the adjusted p-value of 0.05 (t-statistic correction) has been applied to determine significantly regulated proteins in each pairwise comparison. The analysis was performed independently for each sample. In the volcano plot, proteins significantly overexpressed in Pax6+/- compared with Pax6+/+ were marked in red, while those significantly underexpressed were marked in blue. Functional enrichment analyses of significantly modulated proteins were conducted using Enrichr annotations (https://maayanlab.cloud/Enrichr/), encompassing GO Biological Process 2025, Reactome Pathways 2024."],"omics_type":["Proteomics"],"labhead":["Christophe HIRTZ"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["LBPC-PPC, Montpellier University, IRMB CHU Montpellier, INM INSERM, Montpellier, Occitanie, France"],"species":["Mus Musculus (mouse)"],"publication":["42149034 Willems M, Girard M, Feret N, Touchet D, Vialaret J, Kindermans J, Fichter L, Hirtz C, Bremond-Gignac D, Daien V, Delettre C, Pequignot M, Michon F. Sexual Dimorphism Is Associated With Corneal Nerve and Epithelial Alterations and Tear-Film Defects in Pax6 Haploinsufficiency Mouse Model. Invest Ophthalmol Vis Sci. 2026 67(5):39 10.1167/iovs.67.5.39"],"submitter_mail":["j-kindermans@chu-montpellier.fr"],"submitter_affiliation":["PPC - CHU Montpellier Saint-Eloi"],"submitter_country":["France"],"pubmed_abstract":["<h4>Purpose</h4>The purpose of this study was to determine how Pax6 haploinsufficiency alters epithelial maturation, immune balance, sensory innervation, and lacrimal function across the ocular surface, and how these defects affect corneal repair.<h4>Methods</h4>Pax6tm1Ued mice crossed with CMV-Cre were used to generate Pax6+/- animals. Ocular-surface maturation, epithelial organization, immune infiltration, and sensory innervation were assessed by whole-cornea immunostaining. Standardized corneal abrasion was used to evaluate epithelial and neural repair. Corneal RNA sequencing and tear-film proteomics were performed in both sexes to define genotype- and sex-dependent molecular programs.<h4>Results</h4>Pax6+/- mice showed heterogeneous ocular phenotypes, delayed eyelid opening, reduced KRT12, persistent central KRT14 expansion, and a sustained deficit in central proliferation. Immune infiltration was elevated from eyelid opening onward. Corneal nerves were markedly reduced and disorganized, with decreased sensitivity despite minimal trigeminal transcriptional changes. Transcriptomics revealed sex-specific gene-expression patterns converging on inflammation and extracellular-matrix remodeling. After abrasion, closure rates were preserved, but Pax6+/- corneas failed to fully restore normal epithelial identity, territorial patterning, or nerve density. Tear secretion was impaired in a sex-dependent manner, and proteomics showed depletion of structural and antioxidant proteins with exaggerated inflammatory and keratinization responses after injury.<h4>Conclusions</h4>Our model showed that Pax6 haploinsufficiency is associated with epithelial dysmaturation, chronic inflammation, denervation, defective repair, and sex-modulated lacrimal dysfunction. These integrated abnormalities mirror key features of AAK and underline inflammation, neurotrophic support, and tear-film quality as therapeutic targets."],"pubmed_title":["Sexual Dimorphism Is Associated With Corneal Nerve and Epithelial Alterations and Tear-Film Defects in Pax6 Haploinsufficiency Mouse Model."],"pubmed_authors":["Willems Marjolaine M, Girard Mélissa M, Feret Nadège N, Touchet Dylan D, Vialaret Jérôme J, Kindermans Jana J, Fichter Laura L, Hirtz Christophe C, Bremond-Gignac Dominique D, Daien Vincent V, Delettre Cécile C, Pequignot Marie M, Michon Frederic F"],"additional_accession":[]},"is_claimable":false,"name":"Comparative analysis of tear proteomics in PAX6 mutant and control mice of both sexes before and after abrasion","description":"Our team is working on aniridia, an autosomal dominant condition and has used a mouse model. The cornea, the eye’s first avascular and transparent optical surface, is covered by a stratified epithelium that constantly renews itself; any disruption compromises transparency and threatens vision. The tear film, rich in growth factors, protects and nourishes the corneal surface, and proteomic analysis enables global evaluation in normal and pathological states. The transcription factor PAX6 is essential for ocular development, including the lacrimal gland; its mutations cause diverse malformations and, at the corneal level, lead to progressive limbal stem cell deficiency with opacification and fibrosis, along with chronic inflammation and tear film abnormalities. Current treatments for dry eye in this context remain non-specific (artificial tears, cyclosporine, punctal plugs, scleral lenses). Identifying precise qualitative alterations of the tear film is a key step toward designing targeted therapies, such as protein-based eye drops to preserve the cornea in patients with PAX6 mutations. This project is part of a broader study aimed at evaluating the impact of a pathogenic heterozygous PAX6 mutation on the corneal and lacrimal phenotype of mice. We are interested in development, adult phenotype, and healing mechanisms following corneal injury. In this context, we performed a comparative proteomic analysis of tears in PAX6 mutant and control mice of both sexes before and after abrasion.","dates":{"publication":"2026-06-01","submission":"2025-11-10"},"accession":"PXD070553","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:111205","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:10034","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:1589","NEWT:135622","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:36630","NEWT:383379","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:111225","NEWT:7719","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:1912919","NEWT:410658","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:244366","NEWT:1246791","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2709072","NEWT:2853422","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:491","NEWT:460523","NEWT:235443","NEWT:1757312","NEWT:85694","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:472","NEWT:940825","NEWT:529507","NEWT:1071661","NEWT:470","NEWT:5911","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:906914","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:51338","NEWT:575412","NEWT:28112","NEWT:6493","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:9983","NEWT:8655","NEWT:5147","NEWT:28108","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:298176","NEWT:227377","NEWT:1774284","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:443906","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:105487","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:38323","NEWT:475932","NEWT:256318","NEWT:206411","NCBITaxon:6191","NEWT:229533","NEWT:214053","NEWT:28550","NEWT:80863","NEWT:90675","NEWT:52638","NEWT:57075","NEWT:1666905","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:979","NEWT:7370","NEWT:83906","NEWT:99488","NEWT:1134506","NEWT:255470","NEWT:38783","NEWT:6426","NEWT:33090","NEWT:9935","NEWT:287889","NEWT:305959","NEWT:13489","NEWT:29829","NEWT:92867","NEWT:92866","NCBITaxon:3055","NEWT:51750","NEWT:202950","NEWT:441772","NEWT:48106","NEWT:295027","NCBITaxon:11320","NEWT:632957","NEWT:9925","NCBITaxon:9606","NEWT:90690","NEWT:1436183","NEWT:3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