Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization

• Published in: Annals of medicine (Helsinki) Vol. 36; no. 3; p. 232
• Main Authors: Koulu, Markku, Movafagh, Sharareh, Tuohimaa, Jukka, Jaakkola, Ulriikka, Kallio, Jaana, Pesonen, Ullamari, Geng, Yixun, Karvonen, Matti K, Vainio-Jylhä, Elina, Pöllönen, Matti, Kaipio-Salmi, Katja, Seppälä, Helena, Lee, Edward W, Higgins, Rosemary D, Zukowska, Zofia
• Format: Journal Article
• Language: English
• Published: England 2004
• Subjects: Adult; Aged; Animals; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 2 - complications; Diabetic Retinopathy - etiology; Female; Humans; Male; Mice; Middle Aged; Neuropeptide Y - physiology; Rats; Receptors, Neuropeptide Y - physiology; Retinal Neovascularization - etiology
• ISSN: 0785-3890
• DOI: 10.1080/07853890410031236

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.
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.
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.
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.