title: Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization.
abstract: BACKGROUND
  Neuropeptide Y is a sympathetic neurotransmitter, a potent endothelium-derived angiogenic factor and a vascular mitogen. We have studied the role of the functional leucine7 to proline7 polymorphism of the signal peptide region of preproneuropeptide Y (prepro-NPY) as a genetic susceptibility factor for diabetic retinopathy. In addition, we investigated the role of the NPY Y2-receptor as a putative mediator of angiogenic NPY signaling in the retina.
  
  
  METHODS
  Frequencies of proline7 (Pro7) carriers in the prepro-NPY were determined in type 1 and type 2 diabetes patients having retinopathy, in type 2 diabetes patients without retinopathy and in healthy control subjects. The role of Y2-receptor in hyperoxemia-induced retinal neovascularization was investigated in Y2-receptor knockout mice (Y2-/-) and in rats administered Y2-receptor mRNA antisense oligonucleotide.
  
  
  RESULTS
  The carriers having Pro7 in the preproNPY are markedly over-represented among type 2 diabetes patients with retinopathy compared to type 2 diabetes patients without retinopathy and to the population control. Neonatal exposure to hyperoxia resulted in development of retinal neovascularization that was prevented in Y2(-1-) -mice, and significantly inhibited in rats treated with the Y2-receptor antisense oligonucleotide.
  
  
  CONCLUSIONS
  NPY and Y2-receptor play important roles in diabetic retinopathy and retinal neovascularization and are thus potential new targets for drug molecules for treatment of retinopathy.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland. mkoulu@utu.fi
authors.forename: Markku
authors.initials: M
authors.lastname: Koulu
authors.forename: Sharareh
authors.initials: S
authors.lastname: Movafagh
authors.forename: Jukka
authors.initials: J
authors.lastname: Tuohimaa
authors.forename: Ulriikka
authors.initials: U
authors.lastname: Jaakkola
authors.forename: Jaana
authors.initials: J
authors.lastname: Kallio
authors.forename: Ullamari
authors.initials: U
authors.lastname: Pesonen
authors.forename: Yixun
authors.initials: Y
authors.lastname: Geng
authors.forename: Matti K
authors.initials: MK
authors.lastname: Karvonen
authors.forename: Elina
authors.initials: E
authors.lastname: Vainio-Jylhä
authors.forename: Matti
authors.initials: M
authors.lastname: Pöllönen
authors.forename: Katja
authors.initials: K
authors.lastname: Kaipio-Salmi
authors.forename: Helena
authors.initials: H
authors.lastname: Seppälä
authors.forename: Edward W
authors.initials: EW
authors.lastname: Lee
authors.forename: Rosemary D
authors.initials: RD
authors.lastname: Higgins
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zukowska
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009478:Neuropeptide Y / Q000502:physiology*; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D015861:Retinal Neovascularization / Q000209:etiology*
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor