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10 results on '"Physiopathologie des Maladies Oculaires : Innovations Therapeutiques"'

1. Effect of benzalkonium chloride on trabecular meshwork cells in a new in vitro 3D trabecular meshwork model for glaucoma

Author

Christophe Baudouin, Luisa Riancho, Hayet Soualmia, Anne-Laure Raveu, Karima Kessal, Françoise Brignole-Baudouin, Meryem Bouchemi, Christophe Roubeix, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Cell Culture Techniques, Gene Expression, Matrix metalloproteinase, Matrix (biology), Toxicology, Dexamethasone, Proinflammatory cytokine, law.invention, Transforming Growth Factor beta2, 03 medical and health sciences, Benzalkonium chloride, 0302 clinical medicine, Trabecular Meshwork, Confocal microscopy, law, medicine, Humans, Cells, Cultured, Cytoskeleton, ComputingMilieux_MISCELLANEOUS, Matrigel, Interleukin-6, Chemistry, Interleukin-8, Preservatives, Pharmaceutical, Glaucoma, General Medicine, In vitro, Cell biology, Drug Combinations, 030104 developmental biology, medicine.anatomical_structure, Matrix Metalloproteinase 9, Immunology, 030221 ophthalmology & optometry, Proteoglycans, Collagen, Laminin, Trabecular meshwork, Ophthalmic Solutions, Benzalkonium Compounds, medicine.drug
Abstract

Purpose To validate a new culture model of primary human trabecular meshwork cells (p-hTMCs) using Matrigel®, in order to mimic in vitro 3D–TM organization, and to investigate the proinflammatory effect of benzalkonium chloride (BAK) in 3D p-hTMC cultures. Methods p-hTMCs, seeded onto Matrigel®-coated inserts were stimulated with BAK (10− 4%), dexamethasone (DEX) (10− 6 M) or transforming growth factor-beta 2 (TGF-β2) (5 ng/ml) for 48 h and observed with confocal microscopy. The BAK effect at 10− 4% or 5.10− 3% on the gene expressions of interleukin-6 (IL-6), interleukin-8 (IL-8) and matrix metalloproteinase (MMP-9) was investigated using qRT-PCR in 2D and 3D p-hTMC cultures. Results p-hTMCs seeded in Matrigel® were able to organize themselves in a 3D-spatial conformation in the different conditions tested with cross-linked actin network (CLAN) formation in presence of DEX or TGF-β2 and intercellular space contraction with TGF-β2. IL-6 and IL-8 gene expressions increased in presence of BAK in 2D and in 3D p-hTMC cultures. BAK 10− 4% only showed a tendency to stimulate MMP-9 expression in p-hTMCs after 24 h-recovery. Conclusions We investigated this new 3D–TM in vitro model in Matrigel® matrix for pathophysiological and toxicological purposes. It appears as a new promising tool for a better understanding of TM behavior in physiological and stress conditions, as well as toxicological evaluations of antiglaucoma eyedrops and preservatives.

Published
2017
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2. CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex

Author

Borras, C., Canonica, J., Jorieux, S., Abache, T., El Sanharawi, M., Klein, C., Delaunay, K., Jonet, L., Salvodelli, M., Naud, M.C., Arsenijevic, Y., Shalabi, A., Souchaud, L., Behar-Cohen, F., Dinet, V., Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Sorbonne Université (SU), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Université de Lausanne (UNIL), Universitätsklinikum Frankfurt, École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Laboratoire Français du fractionnement et des Biotechnologies, Centre de recherche du CEA/DSV/iBiTec-S/SIMOPRO, Développement, vieillissement et pathologie de la rétine, Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Unit of Retinal Degeneration and Regeneration, Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Laboratoire Français du Fractionnement et des Biotechnologies, and affiliation inconnue

Subjects
[SDV]Life Sciences [q-bio], Blotting, Western, Induced Pluripotent Stem Cells, lcsh:Medicine, Apoptosis, Complement Membrane Attack Complex, Retinal Pigment Epithelium, Real-Time Polymerase Chain Reaction, Article, Cell Line, Tight Junctions, Microscopy, Electron, Transmission, Humans, ddc:610, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Aldehydes, Cell Death, lcsh:R, Recombinant Proteins, eye diseases, Complement cascade, Oxidative Stress, Caspases, Complement Factor H, lcsh:Q, sense organs, Visual system
Abstract

International audience; Age Related Macular Degeneration (AMD) is the first cause of social blindness in people aged over 65 leading to atrophy of retinal pigment epithelial cells (RPE), photoreceptors and choroids, eventually associated with choroidal neovascularization. Accumulation of undigested cellular debris within RPE cells or under the RPE (Drusen), oxidative stress and inflammatory mediators contribute to the RPE cell death. The major risk to develop AMD is the Y402H polymorphism of complement factor H (CFH). CFH interacting with oxidized phospholipids on the RPE membrane modulates the functions of these cells, but the exact role of CFH in RPE cell death and survival remain poorly understood. The aim of this study was to analyze the potential protective mechanism of CFH on RPE cells submitted to oxidative stress. Upon exposure to oxidized lipids 4-HNE (4-hydroxy-2-nonenal) derived from photoreceptors, both the human RPE cell line ARPE-19 and RPE cells derived from human induced pluripotent stem cells were protected from death only in the presence of the full length human recombinant CFH in the culture medium. This protective effect was independent from the membrane attack complex (MAC) formation. CFH maintained RPE cells tight junctions’ structure and regulated the caspase dependent apoptosis process. These results demonstrated the CFH anti-oxidative stress functions independently of its capacity to inhibit MAC formation.

Published
2019
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3. Ocular injuries caused by less-lethal weapons in France

Author

Christophe Chiquet, Carole Burillon, Alain Gaudric, Aurore Chauvin, Jean-François Korobelnik, José-Alain Sahel, Frédéric Mouriaux, Bahram Bodaghi, P. Lebranchu, Gilles Thuret, Pierre Fournier, Max Villain, Jean-Louis Bourges, Frederic Villeroy, Isabelle Cochereau, Carl Arndt, Michel Paques, Laurent Kodjikian, Service d'Ophtalmologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université - Faculté de médecine Pitié Salpétrière, Laboratoire des Sciences du Numérique de Nantes (LS2N), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Department of Ophtalmology, CHU Grenoble, Centre d'Investigation Clinique - Innovation Technologique - INSERM - CHU de Grenoble (CIC-IT Grenoble (CIT803)), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Guy de Chauliac, Service d'ophtalmologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'ophtalmologie [Hopital Bichat - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biomatériaux et remodelages matriciels, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse [CHU - HCL], Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Rennes (UR), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), and Salvy-Córdoba, Nathalie

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Ophthalmology department, Demographic data, Eye injuries, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Retrospective survey, Epidemiology, medicine, Humans, MESH: Eye Injuries, Penetrating/Etiology, Weapons/clasification, Wonds and Injuries/etiology, 030212 general & internal medicine, Young adult, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, General surgery, General Medicine, Middle Aged, medicine.disease, University hospital, Eye Injuries, Penetrating, 3. Good health, 030221 ophthalmology & optometry, Wounds and Injuries, Female, France, Weapons, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Since the introduction of so-called less-lethal weapons in France in the late 1990s, there has been no legal requirement to collect data on injuries induced by kinetic impact projectiles, and no epidemiological surveys have been planned. To estimate the number of patients with ocular injuries caused by the use of these defensive tools, a retrospective survey was sent to all ophthalmology department chairs in French university hospitals, which are where the most severe cases are managed. Demographic data, date of trauma, initial ophthalmological examination and any specialised investigations, initial and immediate surgical management of the injury, follow-up, and visual prognosis were documented and transmitted anonymously.We compiled data from patients seen between February, 2016, and August, 2019 (figure). 43 cases were identified, of which 20 (47%) were managed in Paris. The cases included 38 men and five women, with a median age of 26 years (range 15–59).

Published
2019
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4. Cataracts in a population of Bengal cats in France

Author

Sabine Chahory, Alice Briatta, Alexandre Guyonnet, Aurélie Bourguet, Marie Abitbol, Gilles Chaudieu, Clinique Vétérinaire Beaulieu, Génétique fonctionnelle et médicale, Institut National de la Recherche Agronomique (INRA), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, and Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, genetic structures, 040301 veterinary sciences, [SDV]Life Sciences [q-bio], Buccal swab, Visual impairment, Population, Pedigree chart, Diagnostic Techniques, Ophthalmological, Subcapsular cataract, Cat Diseases, Cataract, 0403 veterinary science, 03 medical and health sciences, Cataracts, Ophthalmology, Prevalence, medicine, Animals, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, CATS, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, General Veterinary, business.industry, [SDV.BA]Life Sciences [q-bio]/Animal biology, 04 agricultural and veterinary sciences, medicine.disease, eye diseases, Pedigree, 030104 developmental biology, Cats, Female, Observational study, France, sense organs, medicine.symptom, business
Abstract

Objective To document the clinical appearance and prevalence of cataracts in a French population of Bengal cats. Methods Two distinct populations of Bengal cats were examined as follows: (i) 51 animals recruited for evaluation of national prevalence of ocular diseases in an observational study conducted between October 2014 and November 2016 at the Alfort ophthalmology unit; (ii) 12 patients referred for cataract diagnosis examined at a veterinary eye clinic located in central France, between December 2014 and February 2016. Buccal swabs or blood samples for DNA analysis were collected from all patients. The pedigrees of the examined Bengal cats were also investigated. Results Cataracts were diagnosed in 23 of 51 (45%) cats in the observational study and in all cats in the referral population, mostly bilaterally. Visual impairment was never reported. Age of subjects affected by cataracts ranged from 3 months to 9.6 years (median: 1.9 years). Cataracts were classified as nuclear cataracts (14 of 23 in the observational group and 12 of 12 in the referral group) with a focal, perinuclear, posterior, or complete nuclear pattern, or posterior polar subcapsular cataracts (10 of 23 only in the observational group). An inherited congenital origin appears to be the most likely hypothesis. The pedigree analysis suggests a hereditary component of cataract formation, but further analyses in a larger population or test matings are needed to determine the exact mode of inheritance. Conclusion Presumed inherited cataracts appear to have a high prevalence in Bengal cats in France. The main manifestations are nuclear or subcapsular form, mostly bilateral, symmetrical, and apparently nonprogressive.

Published
2018
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5. ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy

Author

Rothschild, Pierre-Raphaël, Salah, Sawsen, Berdugo, Marianne, Gelize, Emmanuelle, Delaunay, Kimberley, Naud, Marie-Christine, Klein, Christophe, Moulin, Alexandre, Savoldelli, Michèle, Bergin, Ciara, Jeanny, Jean-Claude, Jonet, Laurent, Arsenijevic, Yvan, Behar-Cohen, Francine, Crisanti, Patricia, Assistance Publique-Hôpitaux de Paris, Department of Ophthalmology, Hôpital Cochin, Paris, France, Métabolisme et physiologie rénale (CRC - UMR_S 1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'opthalmologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Ophthalmology, Université de Lausanne (UNIL), Gérontologie, Institut National de la Santé et de la Recherche Médicale (INSERM), Développement, vieillissement et pathologie de la rétine, Unit of Retinal Degeneration and Regeneration, École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Hôtel-Dieu [Paris], Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), and Université de Lausanne = University of Lausanne (UNIL)

Subjects
Male, [SDV]Life Sciences [q-bio], Science, Fluorescent Antibody Technique, Retinal Pigment Epithelium, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology, Aged, Animals, Biomarkers, Case-Control Studies, Cytoskeleton/metabolism, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2/complications, Diabetic Retinopathy/etiology, Diabetic Retinopathy/metabolism, Diabetic Retinopathy/pathology, Disease Models, Animal, Endothelial Cells/drug effects, Endothelial Cells/metabolism, Endothelial Cells/ultrastructure, Female, Humans, Hypoxia/metabolism, Immunohistochemistry, Middle Aged, Rats, Retinal Pigment Epithelium/drug effects, Retinal Pigment Epithelium/metabolism, Retinal Pigment Epithelium/pathology, Retinal Vessels/drug effects, Retinal Vessels/metabolism, Retinal Vessels/pathology, Retinal Vessels/ultrastructure, rho-Associated Kinases/genetics, rho-Associated Kinases/metabolism, Article, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Hypoxia, ComputingMilieux_MISCELLANEOUS, Cytoskeleton, rho-Associated Kinases, Diabetic Retinopathy, Endothelial Cells, Retinal Vessels, eye diseases, Diabetes Mellitus, Type 2, Medicine, sense organs
Abstract

In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.

Published
2017
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6. Hyperosmolarity and Benzalkonium Chloride Differently Stimulate Inflammatory Markers in Conjunctiva-Derived Epithelial Cells in vitro

Author

Elise Warcoin, Chloé Clouzeau, Anne-Laure Raveu, Luisa Riancho, Françoise Brignole-Baudouin, Christophe Baudouin, David Godefroy, Christophe Roubeix, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), UFR de pharmacie (Université de Bourgogne), Université de Bourgogne (UB), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Godefroy, David

Subjects
0301 basic medicine, Conjunctiva, Cell Survival, [SDV]Life Sciences [q-bio], Enzyme-Linked Immunosorbent Assay, Inflammation, Pharmacology, Cell Line, Proinflammatory cytokine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Benzalkonium chloride, 0302 clinical medicine, NFAT5, medicine, Humans, Chemokine CCL2, ComputingMilieux_MISCELLANEOUS, Interleukin-6, Chemistry, Interleukin-8, Osmolar Concentration, Preservatives, Pharmaceutical, Epithelial Cells, NFAT, General Medicine, Anatomy, Conjunctivitis, Intercellular Adhesion Molecule-1, Intercellular adhesion molecule, Sensory Systems, [SDV] Life Sciences [q-bio], Ophthalmology, 030104 developmental biology, medicine.anatomical_structure, 030221 ophthalmology & optometry, Macrophage migration inhibitory factor, biological phenomena, cell phenomena, and immunity, medicine.symptom, Benzalkonium Compounds, Biomarkers, medicine.drug
Abstract

Tear hyperosmolarity is known to cause ocular surface inflammation in dry eye syndrome. Benzalkonium chloride (BAK), an eyedrop preservative, is known to induce dry eye in long-term-treated patients. Analyzing the modulation of the proinflammatory potential of hyperosmolarity in the presence of BAK on the conjunctiva could give new insights into the effect of this preservative on the disease. In a hyperosmolar model on a conjunctiva-derived cell line, and in the presence of BAK, we evaluated key inflammatory markers [CCL2, IL-8, IL-6, macrophage migration inhibitory factor (MIF) and intercellular adhesion molecule (ICAM)-1] as well as the osmoprotectant element nuclear factor of activated T cells (NFAT)5 using ELISA, RT-qPCR or immunofluorescence staining. Hyperosmolarity highly stimulated CCL2 and NFAT5 in these cells. BAK alone only increased IL-6 expression. The stress-combined condition stimulated CCL2, NFAT5, MIF and IL-8 secretion. ICAM-1 was not modulated by any of the conditions tested. In this model, hyperosmolarity and BAK induced the release of different proinflammatory mediators, and, when combined, they lead to the release of additional inflammatory cytokines. This in vitro study highlights the importance of avoiding long-term ophthalmic treatments containing BAK, as tear film hyperosmolarity can be a result of its detergent action.

Published
2017

7. Scleral and corneal xanthomatous inflammation in a gray mouse lemur ( Microcebus murinus )

Author

Julia Marchal, Eve Laloy, Fabienne Aujard, Charline Alleaume, Meryem El Mrini, Sabine Chahory, Virologie UMR1161 (VIRO), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Mécanismes adaptatifs : des organismes aux communautés (MAOAC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA), Muséum national d'Histoire naturelle (MNHN)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), and Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Microcebus murinus, General Veterinary, Mouse lemur, 040301 veterinary sciences, [SDV]Life Sciences [q-bio], Lemur, Inflammation, 04 agricultural and veterinary sciences, Biology, medicine.disease, biology.organism_classification, Cheirogaleidae, Keratitis, 0403 veterinary science, Pathogenesis, 03 medical and health sciences, 030104 developmental biology, biology.animal, medicine, medicine.symptom, Scleritis, ComputingMilieux_MISCELLANEOUS
Abstract

Bilateral multifocal corneal opacity was detected in a 4.5-year-old male captive gray mouse lemur (Microcebus murinus) without other clinical ocular changes. Histopathological examination revealed a severe diffuse granulomatous scleritis and focal keratitis with intralesional cholesterol, consistent with xanthomatous inflammation. This is the first report of xanthomatous inflammation in a gray mouse lemur. This condition may be the result of systemic factors (lipid metabolism disorders) and/or local predisposing factors such as hemorrhage or inflammation. The pathogenesis in this case could not be fully determined. Further studies on lemurs are required for a better understanding of their lipid metabolism, as well as for diagnosing and evaluating the incidence of xanthomatous inflammation in these species.

Published
2017
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8. Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat

Author

Anne-Laure Raveu, David Godefroy, Elodie Reboussin, Anaïs Sapienza, William Rostène, Julie Degardin, Christophe Baudouin, Céline Boucher, Stéphane Melik Parsadaniantz, Annabelle Réaux-Le Goazigo, Christophe Roubeix, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC) - Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CIC Quinze-Vingts, Assistance publique - Hôpitaux de Paris (AP-HP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, CHU Ambroise Paré, département d'ophtalmologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Service d'Ophthalmologie, and Hôpital Ambroise Paré [AP-HP]

Subjects
Male, Retinal Ganglion Cells, Pathology, genetic structures, [SDV]Life Sciences [q-bio], Ocular hypertension, Glaucoma, Visual deficiency, Functional Laterality, 0302 clinical medicine, Neuroinflammation, Organic Chemicals, ComputingMilieux_MISCELLANEOUS, Tissue macrophage activation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microglia, General Neuroscience, Microfilament Proteins, Up-Regulation, 3. Good health, medicine.anatomical_structure, Neurology, Retinal ganglion cell, Superior colliculi, Optic nerve, Cytokines, Encephalitis, Proto-Oncogene Proteins c-fos, Astrocyte, Cholera Toxin, medicine.medical_specialty, Immunology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Antigens, CD, Glial Fibrillary Acidic Protein, medicine, Animals, Rats, Long-Evans, Visual Pathways, Retina, Neuronal degeneration, Tumor Necrosis Factor-alpha, business.industry, Research, [SCCO.NEUR]Cognitive science/Neuroscience, Calcium-Binding Proteins, [SCCO.NEUR] Cognitive science/Neuroscience, medicine.disease, eye diseases, Rats, Disease Models, Animal, 030221 ophthalmology & optometry, sense organs, business, 030217 neurology & neurosurgery, Optometry
Abstract

International audience; BackgroundGlaucoma is one of the leading causes of irreversible blindness in the world. The major risk factor is elevated intraocular pressure (IOP) leading to progressive retinal ganglion cell (RGC) death from the optic nerve (ON) to visual pathways in the brain. Glaucoma has been reported to share mechanisms with neurodegenerative disorders. We therefore hypothesize that neuroinflammatory mechanisms in central visual pathways may contribute to the spread of glaucoma disease. The aim of the present study was to analyze the neuroinflammation processes that occur from the pathological retina to the superior colliculi (SCs) in a rat model of unilateral ocular hypertension induced by episcleral vein cauterization (EVC).ResultsSix weeks after unilateral (right eye) EVC in male Long-Evans rats, we evaluated both the neurodegenerative process and the neuroinflammatory state in visual pathway tissues. RGCs immunolabeled (Brn3a+) in ipsilateral whole flat-mounted retina demonstrated peripheral RGC loss associated with tissue macrophage/microglia activation (CD68+). Gene expression analysis of hypertensive and normotensive retinas revealed a significant increase of pro-inflammatory genes such as CCL2, IL-1β, and Nox2 mRNA expression compared to naïve eyes. Importantly, we found an upregulation of pro-inflammatory markers such as IL-1β and TNFα and astrocyte and tissue macrophage/microglia activation in hypertensive and normotensive RGC projection sites in the SCs compared to a naïve SC. To understand how neuroinflammation in the hypertensive retina is sufficient to damage both right and left SCs and the normotensive retina, we used an inflammatory model consisting in an unilateral stereotaxic injection of TNFα (25 ng/μl) in the right SC of naïve rats. Two weeks after TNFα injection, using an optomotor test, we observed that rats had visual deficiency in both eyes. Furthermore, both SCs showed an upregulation of genes and proteins for astrocytes, microglia, and pro-inflammatory cytokines, notably IL-1β. In addition, both retinas exhibited a significant increase of inflammatory markers compared to a naïve retina.ConclusionsAll these data evidence the complex role played by the SCs in the propagation of neuroinflammatory events induced by unilateral ocular hypertension and provide a new insight into the spread of neurodegenerative diseases such as glaucoma.

Published
2016
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9. Intraocular pressure reduction and neuroprotection conferred by bone marrow-derived mesenchymal stem cells in an animal model of glaucoma

Author

William Rostène, David Godefroy, José-Alain Sahel, Anaïs Sapienza, Luisa Riancho, Christophe Baudouin, Françoise Brignole-Baudouin, Ivana Ivkovic, Alexandre Denoyer, Julie Degardin, Céline Mias, Valérie Fradot, Serge Picaud, Florian Sennlaub, Stéphane Melik Parsadaniantz, Christophe Roubeix, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement, vieillissement et pathologie de la rétine, Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie cellulaire des neurorécepteurs et physiopathologie neuroendocrinienne, Université Sorbonne Paris Cité (USPC), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Hôpital des Quinze-Vingts, Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Faculté de Pharmacie de Paris ( UPD5 Pharmacie ), Hôpital Ambroise Paré, and Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ )

Subjects
Male, medicine.medical_specialty, Intraocular pressure, Pathology, genetic structures, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Ocular hypertension, Glaucoma, Apoptosis, Mesenchymal Stem Cell Transplantation, Biochemistry, Genetics and Molecular Biology (miscellaneous), [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Animals, Rats, Long-Evans, Cells, Cultured, Intraocular Pressure, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Research, Mesenchymal stem cell, Mesenchymal Stem Cells, Cell Biology, medicine.disease, eye diseases, Rats, 3. Good health, Surgery, Transplantation, medicine.anatomical_structure, Molecular Medicine, Trabecular meshwork, Bone marrow, sense organs, Stem cell, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Introduction Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies. Here, we investigated the potential of MSCs therapy in an glaucoma-like ocular hypertension (OHT) model and decipher in vitro the effects of MSCs on primary human trabecular meshwork cells. Methods Ocular hypertension model was performed by cauterization of 3 episcleral veins (EVC) of Long-Evans male rat eyes. MSCs were isolated from rat bone marrow, amplified in vitro and tagged with quantum dot nanocrystals. Animals were distributed as 1) MSCs group receiving 5.105cells/6μl Minimum Essential Medium and 2) MEM group receiving 6μl MEM (n = 10 each). Injections were performed into the anterior chamber of 20 days-hypertensive eyes and IOP was monitored twice a week for 4 weeks. At the end of experiment, cell distribution in the anterior segment was examined in confocal microscopy on flat mounted corneas. Moreover, we tested in vitro effects of MSCs conditioned medium (MSC-CM) on primary human trabecular meshwork cells (hTM cells) using Akt activation, myosin phosphorylation and TGF-β2-dependent profibrotic phenotype in hTM cells. Results We demonstrated a rapid and long-lasting in vivo effect of MSCs transplantation that significantly reduced IOP in hypertensive eyes induced by EVC. MSCs were located to the ciliary processes and the TM. Enumeration of RGCs on whole flat-mounted retina highlighted a protective effect of MSCs on RGCs death. In vitro, MSC-CM promotes: (i) hTM cells survival by activating the antiapoptotic pathway, Akt, (ii) hTM cells relaxation as analyzed by the decrease in myosin phosphorylation and (iii) inhibition of TGF-β2-dependent profibrotic phenotype acquisition in hTM cells. Conclusions MSCs injection in the ocular anterior chamber in a rat model of OHT provides neuroprotective effect in the glaucoma pathophysiology via TM protection. These results demonstrate that MSCs constitute promising tool for treating ocular hypertension and retinal cell degeneration.

Published
2015
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10. Correlation Between the Inflammatory Marker HLA-DR and Signs and Symptoms in Moderate to Severe Dry Eye Disease

Author

Maeva Deniaud, Luisa Riancho, Mourad Amrane, Françoise Brignole-Baudouin, Christophe Baudouin, Dahlia Ismail, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Soladis, Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Visual analogue scale, [SDV]Life Sciences [q-bio], Arbitrary unit, Meibomian gland, Dry Eye Syndromes, Severity of Illness Index, Gastroenterology, Cornea, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, medicine, Humans, Ocular Surface Disease Index, Fluorescein Angiography, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Clinical Studies as Topic, HLA-DR Antigens, Middle Aged, Flow Cytometry, Fluorescein angiography, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Clinical research, Tears, 030221 ophthalmology & optometry, Female, business, Biomarkers
Abstract

Purpose To investigate correlations of the inflammatory HLA-DR marker with clinical signs and symptoms commonly used to assess dry eye disease (DED) severity. Methods Baseline data were collected from three clinical studies conducted on moderate to severe DED patients. Characteristics of DED were analyzed and correlations were performed in 311 patients. Data were analyzed after treatment with 1 mg/mL cyclosporine (CsA) and vehicle. We quantified HLA-DR by flow cytometry in impression cytology specimens. Results We found HLA-DR significantly increased with diagnosis of Sjogren syndrome (P < 0.0001) and meibomian gland disease (P = 0.0223). The strongest significant correlation was seen with the corneal fluorescein staining (CFS, r = 0.30, P < 0.0001). Significant negative relationships were also found with Schirmer's test (r = -0.20, P = 0.0003) and tear break-up time (TBUT, r = -0.13, P = 0.0226). Correlations were statistically significant with total Ocular Surface Disease Index and visual analog scale scores (r = 0.12, P = 0.0426, and r = 0.14, P= 0.0176, respectively). We found HLA-DR arbitrary units of fluorescence were statistically reduced after CsA treatment compared to vehicle (P = 0.022 and P = 0.021 in two studies). Conclusions In clinical research on DED, discrepancy is often observed between symptoms and signs. We found HLA-DR correlated significantly with CFS clinical signs and to a lower extent Schirmer's test and weakly with TBUT and symptom reporting questionnaires. HLA-DR was reported to be useful for monitoring anti-inflammatory efficacy treatments in DED, which was confirmed with the reduction of HLA-DR while on CsA treatment. Its expression by conjunctival cells has the potential to serve as a biomarker, bridging signs and symptoms in clinical research in DED, but there is still a need for additional validation studies.

Published
2017
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