title: Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema.
abstract: Diabetic macular edema (DME) is the major cause of vision loss in patients affected by diabetic retinopathy. Hyperglycemia and hypoxia represent the key elements in the progression of these pathologies, leading to breakdown of the blood-retinal barrier (BRB). Caffeine, a psychoactive substance largely consumed in the world, is a nonselective antagonist of adenosine receptors (AR) and it possesses a protective effect in various diseases, including eye pathologies. Here, we have investigated the effect of this substance on BRB integrity following exposure to hyperglycemic/hypoxic insult. Retinal pigmented epithelial cells, ARPE-19, have been grown on semi-permeable supports mimicking an experimental model, in vitro, of outer BRB. Caffeine treatment has reduced cell monolayer permeability after exposure to high glucose and desferoxamine as shown by TEER and FITC-dextran permeability assays. This effect is also mediated through the restoration of membrane's tight junction expression, ZO-1. Moreover, we have demonstrated that caffeine is able to prevent outer BRB damage by inhibiting apoptotic cell death induced by hyperglycemic/hypoxic insult since it downregulates the proapoptotic Bax and upregulates the anti-apoptotic Bcl-2 genes. Although further studies are needed to better comprise the beneficial effect of caffeine, we can speculate that it might be used as an innovative drug for DME treatment. J. Cell. Biochem. 118: 2371-2379, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Maugeri
authors.affiliation: Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.|San Raffaele Telematic University of Rome, Rome, Italy.
authors.forename: Agata Grazia
authors.initials: AG
authors.lastname: D'Amico
authors.affiliation: Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Daniela Maria
authors.initials: DM
authors.lastname: Rasà
authors.affiliation: Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.|Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: La Cognata
authors.affiliation: Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saccone
authors.affiliation: Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Federico
authors.affiliation: Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cavallaro
authors.affiliation: Section of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
mesh_terms: D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000378:metabolism*; D015153:Blotting, Western; D002110:Caffeine / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D008269:Macular Edema / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D000072258:Tumor Hypoxia / Q000502:physiology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D002110:Caffeine
keywords: BLOOD-RETINAL BARRIER; CAFFEINE; DIABETIC MACULAR EDEMA