Glucocorticoid Receptor Signaling is Critical for Mouse Corneal Development, Inhibition of Inflammatory Response and Neovascularization of the Cornea
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE213660 | GEO | 2024/06/27
REPOSITORIES: GEO
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Project description:Synthetic glucocorticoids are widely prescribed in the treatment of ocular infections and disorders. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR); however, the molecular and physiological functions of GR signaling in the cornea are poorly understood. In this study, we show that treatment of mice with glucocorticoid eye drops led to a profound regulation of the corneal transcriptome. To determine the global transcriptional profile of GR activity in the cornea, we treated adult wild-type male mice with dexamethasone (a synthetic glucocorticoid) eye drops or vehicle eye drops for 6 hours and then performed RNA sequencing on RNA extracted from whole corneas. All the animals used for this study were adrenalectomized to remove endogenous glucocorticoids. These data demonstrate that a short exposure of glucocorticoids to the cornea results in major changes in the gene expression landscape.
2024-06-27 | GSE213571 | GEO
Project description:Integrity of the cornea, the most anterior part of the eye is indispensable for vision. 45 million individuals are bilaterally blind and another 135 millions have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing with a vertical turnover of seven to fourteen days in many mammals3. Identification of slow cycling cells (label-retaining cells or LRCs) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea4; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in striking opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here, we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. In addition, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells; hence, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. Experiment Overall Design: Expression profile difference between keratinocyte clones from conjunctiva and cornea (3 individual clones in each group)
2008-10-25 | E-GEOD-12604 | biostudies-arrayexpress
Project description:Corneal injuries remain a major cause of consultation in the ophthalmology clinics worldwide. Repair of corneal wounds is a complex mechanism that involves cell death, migration, proliferation, differentiation, and extracellular matrix (ECM) remodeling. In the present study, we used a tissue-engineered, two-layers (epithelium and stroma) human cornea as a biomaterial to study both the cellular and molecular mechanisms of wound healing. Gene profiling on microarrays revealed important alterations in the pattern of genes expressed by tissue-engineered corneas in response to wound healing. Expression of many MMPs-encoding genes was shown by microarray and qPCR analyses to increase in the migrating epithelium of wounded corneas. Many of these enzymes were converted into their enzymatically active form as wound closure proceeded. In addition, expression of MMPs by human corneal epithelial cells (HCECs) was affected both by the stromal fibroblasts and the collagen-enriched ECM they produce. Most of all, results from mass spectrometry analyses provided evidence that a fully stratified epithelium is required for proper synthesis and organization of the ECM on which the epithelial cells adhere. In conclusion, and because of the many characteristics it shares with the native cornea, this human two layers corneal substitute may prove particularly useful to decipher the mechanistic details of corneal wound healing. Primary cultures of human corneal epithelial cells cultivated on BSA (number of replicates: 7), Collagen type I (number of replicates: 2), Collagen type IV (number of replicates: 2), Fibronectin (number of replicates: 2), Tenascin C (number of replicates: 2) and Laminin (number of replicates: 2) matrix. Central, internal and external ring of wounded Tissue-engineered human cornea.
2015-11-25 | E-GEOD-75336 | biostudies-arrayexpress
Project description:To elucidate biological processes underlying the keratocyte, fibroblast, and myofibroblast phenotypes of corneal stromal cells, the gene expression patterns of these primary cultures from mouse cornea were compared with those of the adult and 10-day postnatal mouse cornea.
2007-10-31 | E-GEOD-1867 | biostudies-arrayexpress
Project description:The cornea is the transparent tissue covering the anterior part of the eye. Its main roles are to convey the light toward the retina, and to act as a protective barrier against infection or injury for the eye. The transparency of the cornea is a crucial component of its functionality and is the result of specific architecture and cell arrangements. The inner layer of the cornea is the endothelium, composed of a monolayer of endothelial cells. The next layer is the stroma, representing about two third of the thickness of the cornea, and is mainly composed of a specifically arranged extracellular matrix, secreted by few keratocytes1–4. Finally, the external layer is a life-long renewed pluristratified epithelium. The regulated epithelial homeostasis, crucial to maintain the corneal transparency, relies on stem and progenitor cells5. To coordinate epithelial homeostasis and healing, and to adequately respond to any change in the corneal environment, this tissue is highly innervated6,7. The corneal innervation is mainly composed of A and C sensory fibres whose cell bodies are located in the ophthalmic branch of the trigeminal ganglion8. Those fibres penetrate the corneal stroma from the periphery, as bundles of fibres branching and spreading within the stroma9. When entering in the epithelium, the fibres branche again and radiate horizontally to form the subbasal plexus. Finally, the sensory fibres shift orientation to reach the top of the epithelium, where they end up as free nerve endings6,7. There are three classes of fibres innervating the cornea: the mechano-nociceptors, the cold sensing neurons and the polymodal nociceptors, reacting respectively to mechanical, thermal and chemical stimuli10,11. Stimuli transduction is not the only role of the corneal innervation, as these fibres have a crucial role on epithelial homeostasis through the secretion of trophic factors essential for epithelial cell survival12. Due to its localization, the cornea is highly exposed to ultraviolet radiation and high oxygen tension, making it particularly vulnerable to mitochondrial defects13. These defects can be either inherited or non-inherited. Inherited forms result from mutations in mitochondrial DNA (mtDNA) or nuclear gene defects affecting mitochondrial function14. Inherited mitochondrial dysfunction is a key factor in the progression of Fuchs endothelial corneal dystrophy (FECD) and keratoconus13,15,16. Non-inherited mitochondrial dysfunction, on the other hand, can occur due to spontaneous mtDNA mutations or somatic mutations that accumulate with age, rendering the mitochondrial metabolism less efficient with time17. To date, the impact of inherited mitochondrial dysfunctions on corneal epithelium physiology has not been extensively studied. Case reports have linked mitochondrial diseases to corneal cloudiness18,19, perforation20 and edema21. Furthermore, mitochondrial defect was associated to inflammatory context and ROS production in ocular surface pathologies13,22. Despite these studies, the direct effect of mitochondrial disfunction on corneal biology remains elusive. Among the known pathologies originating from an inherited mitochondrial dysfunction, the dominant optic atrophy (DOA) is an inherited blinding disease caused by the degenescence of the retinal cell ganglions forming the optic nerve23. The mutation of the gene OPA1 is responsible for the majority of the DOA diagnostics. OPA1 gene encodes for a mitochondrial protein involved in the fusion process and is essential to maintain the organelle integrity. Generally, optic neuropathy is the characteristic syndrome for DOA, but a subset of patients, called dominant optic atrophy plus (DOA+), also declare extra-ocular syndromes such as ataxia, deafness and peripheral neuropathies24,25. A mouse model, bearing the OPA1delTTAG mutation, recapitulates the degenerative syndromes encountered in DOA+ patients25.. While DOA is associated with lens cloudiness, no report has linked DOA to ocular surface defects. Here, we investigated the impact of OPA1 delTTAG mutation on mouse cornea as its structure includes a large amout of sensory fibres that are crucial to maintain corneal homeostasis.
2024-07-25 | PXD052337 | Pride
Project description:The cornea is a protective and refractive barrier in the eye crucial for vision. Understanding the human cornea in health, disease and cell-based treatments can be greatly advanced with cornea organoids developed in culture from induced pluripotent stem cells. While a limited number of studies have investigated the single-cell transcriptomic composition of the human cornea, its organoids have not been examined similarly. Here we elucidated the transcriptomic cell fate map of 4-month-old human cornea organoids and human donor corneas. The organoids harbor cell clusters that resemble cells of the corneal epithelium, stroma and endothelium with sub-populations that capture signatures of early developmental states. Unlike the adult cornea where the largest cell population is stromal, the organoids contain large proportions of epithelial and endothelial-like cells. These corneal organoids offer a three-dimensional model to study corneal diseases and integrated responses of different cell types.
2023-01-25 | GSE218123 | GEO
Project description:Central corneal thickness (CCT) exhibits broad variability. We determined the corneal gene expression profile three mouse strains with distinct corneal thickness: C57BLKS/J (88.6 um), SJL/J (123.5 um), and C57BL/6J (100.1 um). Experiment Overall Design: Enucleated eyes from 4 month old mice were dissected in phosphate-buffered saline and a punch of central cornea was collected utilizing a 2-mm biopsy punch. Two central corneal punches (left and right eyes) were pooled from each mouse to form one sample; three samples were analyzed per strain.
2009-09-12 | E-GEOD-14270 | biostudies-arrayexpress
Project description:To elucidate biological processes underlying the keratocyte, fibroblast, and myofibroblast phenotypes of corneal stromal cells, the gene expression patterns of these primary cultures from mouse cornea were compared with those of the adult and 10-day postnatal mouse cornea. Keywords = corneal stroma maturation keratocyte fibroblast myofibroblast TGF beta 1 Keywords: other
2004-10-27 | GSE1867 | GEO
Project description:Integrity of the cornea, the most anterior part of the eye is indispensable for vision. 45 million individuals are bilaterally blind and another 135 millions have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing with a vertical turnover of seven to fourteen days in many mammals3. Identification of slow cycling cells (label-retaining cells or LRCs) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea4; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in striking opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here, we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. In addition, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells; hence, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. Keywords: Cell type comparison
2008-08-29 | GSE12604 | GEO
Project description:Corneal injuries remain a major cause of consultation in the ophthalmology clinics worldwide. Repair of corneal wounds is a complex mechanism that involves cell death, migration, proliferation, differentiation, and extracellular matrix (ECM) remodeling. In the present study, we used a tissue-engineered, two-layers (epithelium and stroma) human cornea as a biomaterial to study both the cellular and molecular mechanisms of wound healing. Gene profiling on microarrays revealed important alterations in the pattern of genes expressed by tissue-engineered corneas in response to wound healing. Expression of many MMPs-encoding genes was shown by microarray and qPCR analyses to increase in the migrating epithelium of wounded corneas. Many of these enzymes were converted into their enzymatically active form as wound closure proceeded. In addition, expression of MMPs by human corneal epithelial cells (HCECs) was affected both by the stromal fibroblasts and the collagen-enriched ECM they produce. Most of all, results from mass spectrometry analyses provided evidence that a fully stratified epithelium is required for proper synthesis and organization of the ECM on which the epithelial cells adhere. In conclusion, and because of the many characteristics it shares with the native cornea, this human two layers corneal substitute may prove particularly useful to decipher the mechanistic details of corneal wound healing.
2015-11-25 | GSE75336 | GEO