Dataset Information

Comparative analysis of tear proteomics in PAX6 mutant and control mice of both sexes before and after abrasion

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Tear

DISEASE(S): Aniridia

SUBMITTER: Jana Kindermans

LAB HEAD: Christophe HIRTZ

PROVIDER: PXD070553 | Pride | 2026-06-01

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	240830_PG_withpool.txt	Txt
	Mouse_F_Cre_post_D1_350ng_S4-C5_1_13127.d.zip	Other
	Mouse_F_Cre_post_D2_350ng_S4-D5_1_13139.d.zip	Other
	Mouse_F_Cre_post_D3_350ng_S4-E5_1_13153.d.zip	Other
	Mouse_F_Cre_post_D4_350ng_S4-F5_1_13166.d.zip	Other

Items per page:

1 - 5 of 92

Publications

Sexual Dimorphism Is Associated With Corneal Nerve and Epithelial Alterations and Tear-Film Defects in Pax6 Haploinsufficiency Mouse Model.

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

Investigative ophthalmology & visual science 20260501 5

<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 corne ...[more]

PMID: 42149034

Similar Datasets

Project description:Congenital aniridia often progresses to vision-threatening aniridia-associated keratopathy (AAK), yet when and how reduced PAX6 dosage destabilizes the ocular surface has remained unclear. Here we combine a conditional Pax6 haploinsufficient mouse with whole-mount imaging, functional assays, and sex-stratified corneal transcriptomics and tear-film proteomics to build an integrated, systems-level picture of disease initiation and progression. Pax6+/− pups show delayed eyelid opening, and from the moment of first environmental exposure the cornea is primed for pathology: leukocytes accumulate by postnatal week two and remain elevated thereafter, epithelial differentiation is mis-specified (KRT12 loss with central expansion of KRT14), and central proliferation is persistently depressed despite grossly normal wound closure. Sensory architecture and function are profoundly impaired, fine epithelial fibers and TRPM8+ terminals are depleted, and corneal sensitivity is reduced, while trigeminal ganglion transcriptomes change little, pointing to a cornea-intrinsic guidance/maintenance failure. Sex emerges as a potent modifier: in otherwise modestly dimorphic wild-type corneas, Pax6 haploinsufficiency drives male- and female-specific gene networks that converge on inflammation and extracellular-matrix remodeling but diverge in metabolic and innate-immune programs; tears mirror and likely reinforce these shifts, with female-biased hyposecretion at baseline and, after abrasion, a failure of Pax6+/− tears to mount the ribosome/translation and axon-guidance response seen in controls, instead exaggerating innate-immune and keratinization pathways. Together, the data recast AAK as a vicious cycle of epithelial dysmaturation, chronic inflammation, and neurotrophic failure amplified by sex-modulated lacrimal changes. By pinpointing early inflammatory priming, a cornea-encoded denervation mechanism, and modifiable tear-film deficits, this work nominates tractable entry points, tempering inflammation, restoring neurotrophic support and reinnervation, and normalizing tear quality, with direct translational relevance to preventing or slowing AAK.

Project description:The cornea is the transparent tissue at the forefront of the eye. Its outermost layer, the corneal epithelium, acts as a protective barrier for the ocular chamber. The cornea is avascular and its homeostasis relies on alternative sources to receive nutrients and growth factors, essential for maintaining its physiological functions and transparency. These sources include the corneal epithelium itself, the innervation and the tear film, collectively forming the corneal microenvironment. Any disruption to this finely balanced system (due to injury, ageing or diseases) can impair corneal transparency and lead to a progressive opacification, ultimately resulting in vision loss. Corneal blindness affects over 28 million people worldwide and represents the fourth leading cause of blindness. Among corneal injuries, abrasions are defined by a transient disruption in the integrity and cohesion of the epithelial barrier and are the most common type of eye injury encountered in clinical practice. Abrasion triggers a complex corneal wound healing process, involving the whole microenvironment, essential to restore transparency. However, a delayed or defective healing can lead to severe complications and visual impairments. Frequently caused by traumatic events, abrasion is also a mandatory step for some refractive surgeries such as photorefractive keratectomy (PRK). Understanding the molecular mechanisms underlying corneal wound healing is thus critical to improve the clinical outcomes and minimize the risk of complications such as haze or delayed epithelial regeneration. The aim of this study is to characterize the temporal dynamics of the tear fluid proteome following PRK and identify molecular signatures associated with corneal epithelial healing. We conducted a prospective cohort study involving longitudinal proteomic analysis of tear samples with mass spectrometry at baseline (preoperative), 30 minutes postoperatively (day 0), and on day 3 after PRK. Ten healthy adult patients undergoing bilateral PRK for myopia correction were included in this study. Corneal epithelial injury was induced by bilateral PRK, a standardized surgical model of epithelial removal followed by laser ablation.