Key result
The Pro7 polymorphism in prepro-NPY was over-represented in type 2 diabetes patients with retinopathy, and Y2-receptor inhibition prevented retinal neovascularization in animal models.
NPY and the Y2-receptor are involved in the pathogenesis of diabetic retinopathy and retinal neovascularization, suggesting they may be potential therapeutic targets.
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NPY Pro7 variant was associated with retinopathy in T2D; leaves open Y2-receptor blockade for neovascularization prevention.
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.
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Koulu et al. (2004) studied Diabetic retinopathy and retinal neovascularization. Proline7 (Pro7) polymorphism in prepro-NPY and Y2-receptor inhibition vs. Non-carriers and wild-type/untreated animals was evaluated on Diabetic retinopathy and retinal neovascularization. The Pro7 polymorphism in prepro-NPY was over-represented in type 2 diabetes patients with retinopathy, and Y2-receptor inhibition prevented retinal neovascularization in animal models.
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