title: VIP Family Members Prevent Outer Blood Retinal Barrier Damage in a Model of Diabetic Macular Edema.
abstract: Diabetic macular edema (DME), characterized by an increase of thickness in the eye macular area, is due to breakdown of the blood-retinal barrier (BRB). Hypoxia plays a key role in the progression of this pathology by activating the hypoxia-inducible factors. In the last years, various studies have put their attention on the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) in retinal dysfunction. However, until now, no study has investigated their protective role against the harmful combined effect of both hyperglycemia and hypoxia on outer BRB. Therefore, in the present study, we have analyzed the role of these peptides on permeability, restoration of tight junctions expression and inhibition of hyperglycemia/hypoxia-induced apoptosis, in an experimental in vitro model of outer BRB. Our results have demonstrated that the peptides' treatment have restored the integrity of outer BRB induced by cell exposure to hyperglycemia/hypoxia. Their effect is mediated through the activation of phosphoinositide 3 kinase (PI3K)/Akt and mammalian mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling pathways. In conclusion, our study further clarifies the mechanism through which PACAP and VIP perform the beneficial effect on retinal damage induced by hyperglycemic/hypoxic insult, responsible of DME progression. J. Cell. Physiol. 232: 1079-1085, 2017. © 2016 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: Neurovisual Science Technology, Catania, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Gagliano
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: D017209:Apoptosis / Q000187:drug effects; D001813:Blood-Retinal Barrier / Q000187:drug effects / Q000473:pathology*; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003930:Diabetic Retinopathy / Q000150:complications* / Q000473:pathology*; D017097:Electric Impedance; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology; D008269:Macular Edema / Q000150:complications* / Q000473:pathology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D062826:Zonula Occludens-1 Protein; D014660:Vasoactive Intestinal Peptide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases