Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization.
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.
Koulu
Markku
M
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland. mkoulu@utu.fi
Movafagh
Sharareh
S
Tuohimaa
Jukka
J
Jaakkola
Ulriikka
U
Kallio
Jaana
J
Pesonen
Ullamari
U
Geng
Yixun
Y
Karvonen
Matti K
MK
Vainio-Jylhä
Elina
E
Pöllönen
Matti
M
Kaipio-Salmi
Katja
K
Seppälä
Helena
H
Lee
Edward W
EW
Higgins
Rosemary D
RD
Zukowska
Zofia
Z
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*
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor