Investigating conjunctival immune pathways in Sjögren and non-Sjögren disease associated dry eye
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE311496 | GEO | 2025/12/01
REPOSITORIES: GEO
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Project description:Lacrimal gland secretory dysfunction in Sjögren syndrome (SS) causes ocular surface desiccation that is associated with increased cytokine expression and number of antigen-presenting cells (APCs) in the conjunctiva. This study evaluated the hypothesis that desiccating stress (DS) alters the percentage and gene expression of myeloid cell populations in the conjunctiva.
2021-07-28 | GSE176390 | GEO
Project description:In 2005, we determined the glyco-gene expression profile of three normal subjects ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27593). This led to information on the biosynthesis of mucin O-glycans and glycoproteins that may be involved in the protection of the ocular surface. The interaction of the most highly expressed glycoprotein identified by the glyco-gene chip, galectin-3, with other ligands at the ocular surface (i.e., mucin O-glycans), is now under intense study in our laboratory, and has lead to a collaboration with another group in the glycobiology field.
2011-04-29 | GSE28941 | GEO
Project description:Investigating conjunctival immune pathways in Sjögren and non-Sjögren disease associated dry eye
| PRJNA1369559 | ENA
Project description:In 2005, we determined the glyco-gene expression profile of three normal subjects ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27593). This led to information on the biosynthesis of mucin O-glycans and glycoproteins that may be involved in the protection of the ocular surface. The interaction of the most highly expressed glycoprotein identified by the glyco-gene chip, galectin-3, with other ligands at the ocular surface (i.e., mucin O-glycans), is now under intense study in our laboratory, and has lead to a collaboration with another group in the glycobiology field. Patients with dry eye disease have an alteration of mucin O-glycans at the ocular surface, but the molecular mechanism(s) leading to this alteration remain unknown. In this experiment we (i) pooled three pathological samples per chip to reduce variability, and (ii) used three additional chips to include pooled control samples (normal subjects). Currently, we have RNA from 9 patients with dry eye disease, which have been divided it in 3 groups (D1, D2, and D3)—each group containing RNA pooled from 3 patients. We request three additional chips to include control samples (normal subjects). At this moment, we have RNA from 9 normal subjects, which have been divided it in 3 groups (N1, N2, and N3)—each group containing RNA pooled from 3 normal subjects. RNA was extracted in Trizol, purified using RNeasy column, and dissolved in water were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to the GLYCOv3 microarrays. Data Analysis was done by Microarray Core (E).
2011-04-29 | E-GEOD-28941 | biostudies-arrayexpress
Project description:Although tropism of SARS-CoV-2 for respiratory tract epithelial cells is well established, an open question is whether the conjunctival epithelium is also a target for SARS-CoV-2. Conjunctival epithelial cells, which express viral entry receptors ACE2 and TMPRSS2, constitute the largest exposed epithelium of the ocular surface tissue, and may represent a relevant viral entry route. To address this question, we generated an organotypic air-liquid-interface model of conjunctival epithelium, composed of progenitor, basal and superficial epithelial cells and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single cell RNA-Seq, with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to SARS-CoV-2 genome expression, a productive infection did not ensure. The early innate immune response to SARS-CoV-2 infection in conjunctival cells was characterised by a robust NF-Kβ activity, alongside evidence of suppression of antiviral interferon signalling. Collectively these data enrich our understanding of SARS-CoV-2 infection at the human ocular surface, with potential implications for the design of preventive strategies such as personal protective equipment.
2022-06-06 | GSE191232 | GEO
Project description:Topical lubrication is the most common remedy for relieving the signs and symptoms of dry eye. However, the therapeutic value of lubricating the ocular surface remains relatively unknown. Here we reveal the restorative properties of the simplest form of lubrication in a mouse model of autoimmune-mediated dry eye. We show topical treatment with PBS rescues corneal stromal architecture through restoring the basement membrane and collagen fiber alignment essential for maintaining corneal transparency. At the single cell level we show keratocytes exhibit significant plasticity under chronic injury, with continuous transition from a homeostatic to inflammatory state, and that lubrication converts these inflammatory cells to a unique reparative phenotype. We further identify IL1b-IL1R1-MAPK signaling as a key pathway driving keratocyte inflammation, and that disruption of the IL1b autocrine amplification loop by lubrication is sufficient to reprogram the inflammatory keratocytes towards the reparative state. Thus, our study underscores the regenerative potential of topical lubrication in dry eye, and reveals fibroblast-targeted therapies as a novel approach to restoring ocular surface health.
2025-01-02 | GSE272700 | GEO
Project description:Topical lubrication is the most common remedy for relieving the signs and symptoms of dry eye. However, the therapeutic value of lubricating the ocular surface remains relatively unknown. Here we reveal the restorative properties of the simplest form of lubrication in a mouse model of autoimmune-mediated dry eye. We show topical treatment with PBS rescues corneal stromal architecture through restoring the basement membrane and collagen fiber alignment essential for maintaining corneal transparency. At the single cell level we show keratocytes exhibit significant plasticity under chronic injury, with continuous transition from a homeostatic to inflammatory state, and that lubrication converts these inflammatory cells to a unique reparative phenotype. We further identify IL1b-IL1R1-MAPK signaling as a key pathway driving keratocyte inflammation, and that disruption of the IL1b autocrine amplification loop by lubrication is sufficient to reprogram the inflammatory keratocytes towards the reparative state. Thus, our study underscores the regenerative potential of topical lubrication in dry eye, and reveals fibroblast-targeted therapies as a novel approach to restoring ocular surface health.
2025-01-02 | GSE272701 | GEO
Project description:Purpose. How vitamin A contributes to the maintenance of the wet-surfaced phenotype at the ocular surface is not well understood. We sought to identify vitamin A responsive genes in ocular surface epithelia using gene microarray analysis of cultures of a human conjunctival epithelial cell line (HCjE) grown with all-trans-retinoic acid (RA). The analysis showed that the membrane-associated mucin MUC16 was induced by RA and that secretory phospholipase A2 Group IIA (sPLA2-IIA), the gene most upregulated by RA, was induced earlier. Since eicosanoids, metabolites of arachidonic acid, which is produced by sPLA2 catalysis of membrane phospholipids, have been demonstrated to affect mucin production, we sought to determine if the sPLA2 induction in HCjE cells was associated with RA induction of MUC16. Methods. HCjE cells were cultured with or without RA for 3, 6, 24 and 48 hours. Complementary RNA prepared from RNA of the HCjE cells was hybridized to human gene chips (HG-U133A; Affymetrix) and analyzed using Rosetta Resolver software. Microarray data on mucin expression were validated by real-time PCR. To investigate whether sPLA2 is associated with RA-induced MUC16 upregulation, HCjE cells were incubated with RA and the broad spectrum PLA2 inhibitor, aristolochic acid (ArA) or the specific sPLA2-IIA inhibitor LY315920, followed by analysis of MUC16 mRNA and protein by real-time PCR and Western blot analysis. Results. After RA addition, 28 transcripts were upregulated and 6 downregulated by over 2.0-fold (p < 0.01) at both 3 and 6 hours (early phase). Eighty gene transcripts were upregulated and 45 downregulated at both 24 and 48 hours (late phase). Group IIA sPLA2, significantly upregulated by 24 hours, and MUC16 were the most upregulated RNAs by RA at 48 hours. sPLA2 upregulation by RA was confirmed by Western blot analysis. When HCjE cells were incubated with RA plus ArA or specific inhibitor of sPLA2-IIA, LY315920, the RA-induced MUC16 mRNA was significantly reduced (p < 0.01). Conclusion. The retinoic acid-associated upregulation of membrane-associated mucin MUC16 at late phase appears to be through sPLA2-IIA. Upregulation of this hydrophilic membrane-associated mucin may be one of the important mechanisms by which vitamin A facilitates maintenance of the wet-surfaced phenotype on the ocular surface. Experiment Overall Design: Time course of retinoic acid treatment of human conjunctival epithelial cells: 0 (control), 3, 6, 12, 24, and 48 hours. 2 samples per time point.
2007-12-12 | E-GEOD-2835 | biostudies-arrayexpress
Project description:Dry eye disease affects millions worldwide and can result from age-related lacrimal gland (LG) dysfunction, which correlates with a decline in LG secretory cell function and chronic inflammation. This study investigates the potential of calorie restriction (CR) to maintain LG and ocular surface health. Female C57BL/6J mice were subjected to 40% CR for 4 months (start age 6/7 until 10/11M) and compared to mice receiving food ad libitum (AL). LGs bulk RNA sequencing was performed, and fastq files were uploaded on ROSALIND® for processing. Differentially Expressed Genes (DEGs) were analyzed in Metascape to identify the biological pathways significantly modified by CR, and findings were validated. RNA sequencing of LGs subjected to CR compared to ad libitum revealed 589 significant DEGs, with 259 downregulated and 330 upregulatedPathways enriched in upregulated DEGs suggested increase in secretory functions and lipid metabolism, while pathways enriched in downregulated DEGs are related to immune cell activation, the adaptive immune system, extracellular matrix remodeling, and metalloproteinases. These changes were validated by individual qPCR. CR also decreased the age-related dry eye phenotype compared to the ad libitum group. Our results suggest that CR can maintain the health of the LG and ocular surface by reducing inflammation and supporting the LG's secretory function.
2025-12-04 | GSE281747 | 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