Lacrimal gland myoepithelial cells are altered in a mouse model of dry eye disease
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PROVIDER: PRJNA633545 | ENA |
REPOSITORIES: ENA
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Project description:The purpose of this study was to determine the pathogenic changes that occur in myoepithelial cells (MECs) from lacrimal glands of a mouse model of Sjogren’s syndrome. MECs were cultured from lacrimal glands of C57BL/6J (wild type, WT), and thrombospondin 1 knockout null (TSP1 -/- ) mice. We used microarray to analyzed the differential expression of genes in cultured MECs of TSP1-/- and wild type (WT) mice.
2020-06-25 | GSE150771 | GEO
Project description:Purpose: Identify the differentially expressed circular RNA (circRNA) and elucidate their potential function in AQP5 knockout (AQP5-/-) mice with primary dry eye phenotype. Methods: A slit lamp examination was performed on AQP5 knockout mice to assess corneal epithelial defect by fluorescein sodium staining. Hematoxylin-eosin staining and transmission electron microscope analysis were performed to access the structure of lacrimal gland epithelial cells. The expression profiles of circRNA and messenger RNA (mRNA) were determined by microarray analysis. The selected circRNA was verified by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict biological functions and potential pathways of parental genes involved in lacrimal gland epithelial cell changes. According to the bioinformatics analysis of identified circRNA, we can predict a circRNA-miRNA-mRNA network. Results: AQP5-/- mice exhibit spontaneous dry eye symptoms. AQP5 deficiency obviously changes the structure of lacrimal gland epithelial cells. Analysis showed that compared to AQP5+/+ mice, 30 circRNAs in the lacrimal glands of AQP5‑/- mice had differential expression (fold change ≥ 2.0, P < 0.05). Nine upregulated circRNAs were identified by qRT-PCR; nine upregulated validated circRNAs, 40 altered microRNAs (miRNAs), and nine upregulated mRNAs were involved in the network analysis. KEGG analysis showed these nine target genes were expressed in phagosomes. Conclusions: AQP5-/- mice have primary and stable dry eye phenotypes from birth. The study identified different expressed circRNAs in lacrimal glands between AQP5-/- and AQP5+/+ mice, predicting a circRNA-miRNA-mRNA network of phagosomes. CircRNA likely plays an important role in lacrimal gland epithelial cell pathogenesis. Therefore, it is reasonable to use circRNA as a potential therapeutic target for dry eyes.
2020-09-23 | GSE149832 | GEO
Project description:The purpose of this study was to determine the pathogenic changes that occur in myoepithelial cells (MECs) from lacrimal glands of a mouse model of Sjögren syndrome. MECs were cultured from lacrimal glands of C57BL/6J [wild type (WT)] and thrombospondin 1 null (TSP1-/-, alias Thbs1-/-) mice and from mice expressing α-smooth muscle actin-green fluorescent protein that labels MECs. MECs were stimulated with cholinergic and α1-adrenergic agonists, vasoactive intestinal peptide (VIP), and the purinergic agonists ATP and UTP. Then intracellular [Ca2+] was measured using fura-2, and contraction was observed using live cell imaging. Expression of purinergic receptors was determined by Western blot analysis, and mRNA expression was analyzed by microarray. The increase in intracellular [Ca2+]I with VIP and UTP was significantly smaller in MECs from TSP1-/- compared with WT mice. Cholinergic agonists, ATP, and UTP stimulated contraction in MECs, although contraction of MECs from TSP1-/- mice was reduced compared with WT mice. The amount of purinergic receptors P2Y1, P2Y11, and P2Y13 was significantly decreased in MECs from TSP1-/- compared with WT mice, whereas several extracellular matrix and inflammation genes were up-regulated in MECs from TSP1-/- mice. We conclude that lacrimal gland MEC function is altered by inflammation because the functions regulated by cholinergic agonists, VIP, and purinergic receptors are decreased in TSP1-/- compared with WT mice.
| S-EPMC7520664 | biostudies-literature
Project description:Comparison of the effect of ocular surface desiccation and the lack of adaptive immunity (T and B cells) on gene expression in the trigeminal ganglia. Eight-week-old female mice of both strains were either operated on day 1 (either bilateral extraorbital lacrimal gland excision or sham surgery) and allowed to develop a dry eye state until day 10, when they were euthanized and the trigeminal ganglia were excised for RNA extraction. The two trigeminal ganglia of each mouse were pooled in one sample. There were 12 samples in total (2 x 2 design, 2 strains, 2 treatments).
2024-04-01 | E-MTAB-13945 | biostudies-arrayexpress
Project description:Background: The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods: We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix ® gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results: The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions: Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.
2017-01-03 | GSE89827 | GEO
Project description:In humans, the lacrimal gland produces the aqueous component of the tear film, which e.g. moistens and nourishes the ocular surface to maintain ophthalmic health. Decreased production of the aqueous component leads to the development of dry eye disease, which affects over 250 million people worldwide. Despite the impact on patients, the availability of primary human material to study underlying disease mechanisms is severely constrained. Here, we report the development of an immortalized human lacrimal gland epithelial cell line that improves accessibility to study the molecular pathogenesis-mechanisms of dry eye disease and link them to causal treatments.
2024-04-17 | GSE239464 | GEO
Project description:In this study, we transferred gut microbiota of SS-like autoimmune dry eye disease model mice to conventional B6 mice (NOD-FMT). After the transfer, NOD-FMT mice experienced a dramatic change in the gut microbiomes and showed clinicopathological features of SS, including increased corneal fluorescein staining score, decreased tear production, elevated levels of IL-6 mRNA, decreased levels of MUC5AC mRNA encoding mucin. Additionally, we observed that NOD-FMT mice shared stereotypic B cell receptor (BCR) clonotypes with a much higher frequency compared to control group. B cell clones encoding these stereotypic BCR clonotypes developed and expanded locally in the lacrimal gland, and achieved systemic presence in certain clonotypes.
2024-06-26 | GSE263577 | GEO
Project description:The graft-versus-host disease (GVHD) associated dry eye disease usually leads to refractory pain and visual impairment with limited treatments currently. Here we found exosome derived from mesenchymal stromal cell (MSC-exo) administered as eye drops significantly alleviates GVHD-associated dry eye disease in human and mouse models. To find out the essential elements during exosome treatment, we performed miRNA sequencing of exosomes derived from MSCs and L929 cells, and identified miR-204 in MSC-exo benefited the recovery of dry eye, which targeted IL-6/IL-6R/Stat3 signaling. Blockade of miR-204 abolished the therapeutic effect of MSC-exo while miR-204 overexpression from L929-exo markedly attenuates dry eye. Thus MSC-exo eye drops are efficacious in treating GVHD-associated dry eye and highlight miR-204 as a potential therapeutic agent.
2022-01-19 | GSE166585 | GEO
Project description:To analyze the gene expression of mouse embryonic lacrimal gland and its developmental related organs such as harderian gland and eye lid. We performed microarray using them.
2017-08-13 | GSE71867 | GEO
Project description:Rabbit Dry Eye Diesease model induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands Male Dutch-Belted rabbits. The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. The transcriptome of full-thickness’s conjunctival tissue from rabbits with DED and from normal controls was determined using microarrays. DED induced large-scale changes in gene transcription involving 5,184 genes (22% of the total). Differentially expressed genes could be segregated into: functional modules and clusters; altered pathways; functionally linked genes; and groups of individual genes of known or suspected pathophysiological relevance to DED. A common feature of these subgroups is the breadth and magnitude of the changes that encompass ocular immunology and essentially all aspects of cell biology. Prominent changes concerned innate and adaptive immune responses; ocular surface inflammation; at least 25 significantly altered signaling pathways; a large number of chemokines; cell cycle; and apoptosis. Comparison of our findings to the limited extant transcriptomic data from DED patients associated with either Sjogren’s syndrome or non-Sjogren’s etiologies revealed a significant correlation between human and rabbit DED transcriptomes. Our data, establishing the large-scale transcriptomic changes of DED and their potential similarity to the human, underscore the enormous complexity of DED; establish a robust animal model of DED; will help expand our understanding of its pathophysiology; and could guide the development of successful therapeutic strategies.
2021-03-30 | GSE171043 | GEO