title: Choroidal mast cells in retinal pathology: a potential target for intervention.
abstract: Mast cells are important in the initiation of ocular inflammation, but the consequences of mast cell degranulation on ocular pathology remain uncharacterized. We induced mast cell degranulation by local subconjunctival injection of compound 48/80. Initial degranulation of mast cells was observed in the choroid 15 minutes after the injection and increased up to 3 hours after injection. Clinical signs of anterior segment inflammation paralleled mast cell degranulation. With the use of optical coherence tomography, dilation of choroidal vessels and serous retinal detachments (SRDs) were observed and confirmed by histology. Subconjunctival injection of disodium cromoglycate significantly reduced the rate of SRDs, demonstrating the involvement of mast cell degranulation in posterior segment disorders. The infiltration of polymorphonuclear and macrophage cells was associated with increased ocular media concentrations of tumor necrosis factor-α, CXCL1, IL-6, IL-5, chemokine ligand 2, and IL-1β. Analysis of the amounts of vascular endothelial growth factor and IL-18 showed an opposite evolution of vascular endothelial growth factor compared with IL-18 concentrations, suggesting that they regulate each other's production. These findings suggest that the local degranulation of ocular mast cells provoked acute ocular inflammation, dilation, increased vascular permeability of choroidal vessels, and SRDs. The involvement of mast cells in retinal diseases should be further investigated. The pharmacologic inhibition of mast cell degranulation may be a potential target for intervention.
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France; University of Paris Descartes, Sorbonne Paris Cité, Sorbonne Universities, UPMC Univ Paris 06, Cordeliers Research Center, F-75006, Paris, France; Department of Ophthalmology, Hôtel-Dieu of Paris, Assistance Publique Hôpitaux de Paris, Sorbonne Paris Cité, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Bousquet
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Thillaye-Goldenberg
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France.
authors.forename: Viera
authors.initials: V
authors.lastname: Lorena
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castaneda
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France.
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Naud
authors.affiliation: Department of Ophthalmology of Lausanne University, Jules Gonin Ophthalmic Hospital, Lausanne, Switzerland.
authors.forename: Ciara
authors.initials: C
authors.lastname: Bergin
authors.affiliation: Technologic platform of phenotypage of small animals, IFR65/IRSSA, Saint-Antoine Hospital, Paris, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Besson-Lescure
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France; University of Paris Descartes, Sorbonne Paris Cité, Sorbonne Universities, UPMC Univ Paris 06, Cordeliers Research Center, F-75006, Paris, France; Department of Ophthalmology of Lausanne University, Jules Gonin Ophthalmic Hospital, Lausanne, Switzerland.
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.affiliation: INSERM UMRS1138, Team 17: Physiopathology of Ocular Diseases: From Physiopathology to Clinical Developments, Paris, France. Electronic address: yvonne.de_kozak@crc.jussieu.fr.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Kozak
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects*; D018925:Chemokines / Q000378:metabolism; D002829:Choroid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D018925:Chemokines; D016207:Cytokines; D003189:p-Methoxy-N-methylphenethylamine