Biology subjects

Daien, V.

Publications and source records attributed to Daien, V..

3 recordsLinked to original sources

bioRxiv2025

Reversible multiscale corneal sexual dimorphism orchestrates neuro-epithelial coupling and tear proteome composition

Donor-recipient sex mismatch is an under-recognized risk factor for corneal graft rejection, yet the biological underpinnings at the ocular surface remain undefined. We hypothesized that sex hormones coordinately tune the tear-nerve-epithelium axis and that androgen exposure could normalize sex-linked differences relevant to alloimmune risk. We profiled 12-week-old mice in three hormonal contexts, i.e. male, female, and testosterone-treated female, combining tear biochemistry and label-free proteomics with epithelial lineage dynamics, in vivo sensory function, and corneal/trigeminal transcriptional readouts. Tear collection rate was comparable across groups, but total tear protein was reduced in females. Proteomics revealed extensive sex differences in extracellular composition, spanning lipid transport, protease-antiprotease balance, complement activity, and secretory/mucin pathways. Epithelial analyses showed sex-linked differences in progenitor output and spatial deployment, and sensory metrics indicated divergent innervation architecture and function. Across modalities, androgen supplementation in females shifted molecular and physiological profiles toward the male state, attenuating nearly all dimorphic signals, demonstrating that close to all sexual dimorphism observed here is reversible by testosterone and reflects an actively maintained endocrine state rather than a fixed developmental program. Complementary metabolite profiling provides a sex-stratified atlas of free modified nucleosides in tears, positioning extracellular epitranscriptomic markers as accessible indicators of hormonal context. Together, these results establish a multiscale, hormone-responsive sexual dimorphism at the ocular surface and offer a mechanistic framework linking sex and endocrine status to parameters that influence graft integration. They motivate sex-aware biomarkers, stratification by hormonal context in diagnostics and trials, and therapeutic strategies, including androgenic modulation, to mitigate the elevated rejection risk associated with sex mismatch in corneal transplantation.

physiology↗

bioRxiv2025

Integrated tear proteomics define the molecular blueprint of corneal epithelial repair

The tear film plays an essential role in corneal protection and regeneration following injury. Although the cornea is a structurally conserved organ across terrestrial vertebrates, the extent to which tear film mediated wound healing responses are evolutionarily conserved remains unclear. This study aimed to identify core and species-specific molecular pathways activated in the tear film during corneal wound healing in humans and mice. We conducted a meta analysis of tear proteomic datasets from human subjects undergoing photorefractive keratectomy (PRK) and mice subjected to mechanical corneal abrasion. Differentially expressed proteins were identified and subjected to Reactome and Gene Ontology (GO) enrichment analyses to determine conserved and divergent biological responses. Approximately one third of the tear film proteomic response to corneal injury was conserved across species. Shared upregulated pathways included complement activation, actin cytoskeletal remodeling, protein synthesis, and acute inflammatory responses. Simultaneously, pathways related to adaptive immunity, proteolysis, and general metabolism were consistently downregulated. Human specific responses were enriched in secretory pathways, vesicle trafficking, and immune surveillance, whereas murine specific responses highlighted mitochondrial activation, oxidative metabolism, and stress adaptation. These distinctions reflect species dependent physiological strategies in managing epithelial repair. Our findings reveal a conserved molecular framework that governs corneal wound healing across species, with notable species specific adaptations. This cross species comparison underscores the translational relevance of tear film analysis and supports the development of targeted therapies tailored to human specific wound healing mechanisms in ocular surface disease.

physiology↗

bioRxiv2025

Temporal analysis of tear fluid proteome reveals critical corneal repair events after photorefractive surgery

Corneal epithelial wound healing is a complex and finely orchestrated process critical for restoring visual acuity following injury or surgery. Photorefractive keratectomy (PRK), a common refractive surgical procedure, provides an ideal clinical model to study this process. Here, we employed advanced proteomic analysis to comprehensively map the dynamic changes in the tear fluid proteome at distinct phases following PRK. Our findings revealed significant alterations in nearly 45% of the tear proteome, highlighting temporally distinct molecular signatures. Immediately post-injury, a robust but controlled anti-inflammatory response coincided with pronounced upregulation of protein synthesis and cellular stress-management pathways. Subsequently, at day three, the molecular landscape shifted toward sustained epithelial regeneration, extracellular matrix remodeling, and controlled inflammation resolution. By delineating these critical and temporally compartmentalized molecular events, this study identifies novel tear-based biomarkers indicative of corneal healing efficacy and provides essential insights into potential therapeutic targets for improving clinical outcomes in corneal wound healing and ocular surface disorders.

physiology↗