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: Markku Koulu, Sharareh Movafagh, Jukka Tuohimaa, Ulriikka Jaakkola, Jaana Kallio, Ullamari Pesonen, Yixun Geng, Matti K Karvonen, Elina Vainio-Jylhä, Matti Pöllönen, Katja Kaipio-Salmi, Helena Seppälä, Edward W Lee, Rosemary D Higgins, Zofia Zukowska
• Journal: Annals of medicine (Ann Med) Vol. 36 Issue 3 Pg. 232-40 ( 2004) ISSN: 0785-3890 [Print] England
• PMID: 15181979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neuropeptide Y
• Receptors, Neuropeptide Y
• neuropeptide Y2 receptor

Topics

• 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)