Ontology highlight
ABSTRACT:
PROVIDER: PRJNA597168 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10756900.fastq.gz | Fastqsanger.gz | |||
| SRR10757000.fastq.gz | Fastqsanger.gz | |||
| SRR10757100.fastq.gz | Fastqsanger.gz | |||
| SRR10756901.fastq.gz | Fastqsanger.gz | |||
| SRR10757001.fastq.gz | Fastqsanger.gz |
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Project description:Tears are mainly secreted from the lacrimal gland under precise controls by autonomic neural response to external sensory and psychogenic emotional stimulation. Dynamic volume and compositional changes of tears may lead to development of dry eye disease. The role of sympathetic nerve system (SNS) in controlling tear secretion and the noradrenergic neural circuit projecting from brain to lacrimal gland remain unexplored. Here, we discovered the dense sympathetic innervation of mouse lacrimal gland and investigated its physiological role in regulating tear production. In response to dry eye stimuli, SNS became overactivated with high noradrenaline (NA) in the lacrimal gland. Using gain- and loss-of-functional approaches, including pharmacologic, surgical, chemogenetic manipulations, and genetic knockout mice of specific adrenergic receptors, we demonstrated that both SNS ablation and NA blockage markedly increased tear volume and alleviated dry eye diseases. Mechanistically, activation of SNS released NA to reduce tear secretion through binding to α1a-adrenergic receptor (Adra1a) that targeted mitochondrial Ucp2 in the acinar and myoepithelial cells of the lacrimal gland. Consequently, antagonization of NA and Ucp2 markedly increased tear secretion. Using a retrograde neuronal tracing technique in combination with physiologic experiments of tear reduction and hypersecretion, we identified a novel noradrenergic neural circuit projecting from the brain locus coeruleus to the lacrimal gland and the orchestrated controlling of parasympathetic and sympathetic nervous system for tear secretion. Together, our data define a novel NA-Adra1a-Ucp2 signaling pathway as a gatekeeper mechanism for controlling tear secretion from the lacrimal gland. These findings provide novel mechanistic insights into sympathetic role in tear secretion and potential therapeutic options for treatment of dry eye disease.
2025-05-08 | GSE224484 | GEO
Project description:Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. We have shown that oral administration of tributyrin, a prodrug form of butyrate, is protective of the ocular surface in mice undergoing desiccating stress. To gain insight into the mechanism, we analyzed gene expression in conjunctival tissue from mice treated with either tributyrgn or vehicle control.
2022-02-07 | GSE195578 | GEO
Project description:Tears are a biological fluid that has diagnostic potential for ocular diseases. Extracellular vesicles (EVs), wildly detected in various biofluids including tears, are nanoparticles released by living cells and considered as promising detection sources for non-invasive liquid biopsy. Understanding the roles of tears and tear-EVs in ocular diseases such as dry eye can facilitate the studies of clinical diagnosis, which usually entails detecting such liquid objects with a rapid and effective method. In this study, we utilized a mass spectrometry based strategy to analyze peptidome/proteome profiles of tear and EVs for rapid dry eye diagnosis. Nano-sized EVs were isolated from tears of either healthy control (HC) individuals or dry eye syndrome (DES) patients, and the tear compositions were further analyzed by tracking their fingerprints with matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS). The fingerprints of tear-EVs could be observed in a dose-dependent manner as well as tears, allowing comparing their discriminant peaks between tears and EVs. By analyzing these peaks, the fingerprints of both tear and tear-EVs were showed to have a capability of distinguishing DES patients from HC donors, and providing an efficient way for screening potential DES biomarkers. The proposed tear and EV fingerprinting approach is expected to be a potential tool in rapid diagnosis of ocular disease and in-depth researches of pathogenesis.
2020-08-20 | PXD020217 | Pride
Project description:Corneal architecture is essential for vision and is greatly perturbed by the absence of tears due to the highly prevalent disorder dry eye. With no regenerative therapies available, pathological alterations of the ocular surface in response to dryness, including persistent epithelial defects and poor wound healing, result in lifelong morbidity. Here, using a mouse model of aqueous-deficient dry eye, we reveal that topical application of the synthetic tear protein lacripep reverses the pathological outcomes of dry eye through restoring the extensive network of corneal nerves that are essential for tear secretion, barrier function, epithelial homeostasis and wound healing. Intriguingly, the restorative effects of lacripep occur despite extensive immune cell infiltration, suggesting tissue reinnervation and regeneration can be achieved under chronic inflammatory conditions. In summary, our data highlight lacripep as a first-in-class regenerative therapy for returning the cornea to a near homeostatic state in individuals who suffer from dry eye.
2022-07-18 | GSE208297 | GEO
Project description:Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammation and damage to exocrine glands, leading to symptoms such as dry eye and reduced tear production. The NF-κB signaling pathway plays a critical role in the inflammatory processes underlying pSS. The aims of the present in vivo study were to investigate the role of NF-κB signaling in lacrimal gland damage and tear secretion in the NOD/Ltj mouse, and to explore the therapeutic potential of NF-κB inhibition. The animal model was established using NOD/Ltj mouse and lacrimal gland pathological change was showed by H&E. Bioinformatics analysis was conducted through RNA sequencing (RNA-seq) and confirmed by RT-qPCR and Western blot. The NOD/Ltj mouse were treated with NF-κB inhibitor JSH-23. Tear secretion assays, ELISA, TUNEL staining, immunofluorescence, immunohistochemistry, and flow cytometry were employed to assess the role of NF-κB signaling in tear production, inflammatory cytokine expression, cell apoptosis, differentially expressed genes (DEGs), and cell differentiation in lacrimal gland damage in pSS mouse. NF-κB signaling was significantly activated in NOD/Ltj mouse lacrimal gland and pSS-related dry eye. NF-κB blockage decreased cell apoptosis, reduced inflammatory cytokine expression, and inhibited Th17 cell differentiation in NOD/Ltj mouse lacrimal glands, as well as restored tear production and normalized the expression of DEGs CARD14 and CCL19. NF-κB signaling played a pivotal role in lacrimal gland damage in pSS model NOD/Ltj mouse by involvement of cell apoptosis, inflammatory cytokine expression and Th17 cell differentiation. Targeting NF-κB signaling may offer a promising therapeutic approach for managing pSS-related dry eye.
2025-08-25 | GSE306385 | GEO
Project description:The lacrimal gland (LG) is essential for tear secretion and plays a critical role in dry eye disease (DED). This study utilized single-nucleus RNA sequencing (snRNA-seq) to investigate the cellular diversity of the LG in both normal and DED conditions.
2025-05-08 | GSE280211 | GEO
Project description:Although tear replacement and anti-inflammatory treatments have been thoroughly investigated, a method to induce epithelial restoration is lacking. Here, we asked whether WNT signaling activation via an antibody-based WNT mimetic platform might activate lacrimal gland acinar cells and restore tear secretion. Transcriptional and cellular changes were investigated using single cell sequencing. In a mouse model of dry eye disease, and intra-lacrimal gland treatment with a WNT mimetic targeting FZD1, 2, and 7 reversed aqueous tear deficiency. After excretory duct ligation damage, WNT mimetic treatment promoted acinar cell restoration and increased detectable tear volume production. We demonstrate a role for WNT signaling in acinar cell proliferation, and scRNA-seq revealed that the WNT mimetic promotes pathway activation and proliferation in injury-induced states. Our findings extend the potential for WNT pathway activation via a ligand mimetic platform to lacrimal gland regeneration.
2025-06-10 | GSE295860 | GEO
Project description:Glycosylation of proteins is one of the most common post-translational modification (PTM) and plays important regulatory functions in diverse biological processes such as protein stability or cell signaling. Accordingly, glycoproteins are also a consistent part of the human tear film proteome maintaining the proper function of the ocular surface and forming the first defense barrier of the ocular immune system. Irregularities in the glycoproteomic composition of the tear film might promote development of chronic eye diseases indicating glycoproteins as valuable source for biomarker discovery or drug target identification. The present study aimed to develop a lectin-based affinity method for the enrichment and concentration of tear glycoproteins/glycopeptides and the characterization of their specific N-glycosylation sites by high-resolution mass spectrometry (MS). For method development and evaluation, we accumulated first native glycoproteins from human tear sample pools and assessed the enrichment efficiency of different lectin column systems by 1D gel electrophoresis and specific protein stainings (Coomassie and glycoproteins). The best-performing multi-lectin column system (comprising the four lectins ConA, JAC, WGA and UEA I, termed as 4L) was applied for glycopeptide enrichment from human tear sample digests followed by MS-based detection and localization of their specific N-glycosylation sites. As main result, the present study identified in total 26 N glycosylation sites of 11 N-glycoproteins in tear sample pools of healthy individuals (n=3 biological sample pools). Amongst others, we identified tear film proteins lactotransferrin (N497 and N642, LTF), Ig heavy chain constant α-1 (N144 and 340, IGHA1), prolactin-inducible protein (N105, PIP) as well as extracellular lacritin (N105, LACRT) as highly reliable and significant N glycoproteins, which were already associated with the pathogenesis of various chronic eye diseases such as the dry eye syndrome (DES). In conclusion, the results of the present study will serve as important tear film N-glycoprotein catalogue for future studies focusing the human tear film and ocular surface-related inflammatory diseases.
2023-01-25 | PXD038280 | Pride
Project description:The cornea is the transparent tissue on the anterior surface of the eye. It is notably composed of a squamous stratified epithelium that forms a barrier protecting the ocular chamber. As the cornea is avascular, the delivery of nutrients and growth factors, required for corneal physiology, is essential. These nutrients and factors come from 1) the epithelium itself, 2) the innervation, and 3) the tear film, which together form the corneal microenvironment. Disturbances of this microenvironment, in the context of injury, aging or corneal pathology, can lead to progressive corneal opacification, resulting in blindness. More than 28 million people suffer from mono- or bilateral corneal blindness, making it the fourth cause of blindness worldwide. Corneal abrasion is the most common eye injury encountered in clinics, but poorly studied, making it a major issue in ophthalmology. It is characterized by a transient rupture in the integrity and cellular cohesion of the epithelial barrier, which are brought back thanks to a corneal wound healing process. The aim of this study is therefore to highlight the molecular impact of corneal abrasion on the microenvironment, and more specifically on the tear film. We performed a longitudinal study to identify a specific proteome of tears before and after corneal abrasion in mice. The corneal abrasion was performed unilaterally on female mice. Tear fluid samples were collected from the wounded eye and the contralateral eye before corneal abrasion and during the wound healing process up to 24hrs post-abrasion.
2025-11-10 | PXD061492 | Pride