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

Abstract

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.

Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations

“…Interestingly, the polymorphism exists with a relatively high frequency in Finnish and Swedish populations but low frequency in other ethnic populations (18,19). In the past 7 years, several genetic studies indicate that polymorphism is associated with the development of T2D (20), retinopathy (21,22), and enhanced carotid atherosclerosis (23). Moreover, there is a report indicating that Leu7Pro polymorphism confers susceptibility to the development of nephropathy and coronary heart disease (CHD) in Finnish female T1D patients (24).…”

NPY in rat retina is present in neurons, in endothelial cells and also in microglial and Müller cells

“…NPY has been reported to directly stimulate endothelial cell proliferation and migration (Ekstrand et al, 2003;Ghersi et al, 2001;MarionAudibert et al, 2000;Zukowska-Grojec et al, 1998a,b). In the retina, some evidences have shown that NPY and Y 2 receptors are involved in development of diabetic retinopathy and retinal neovascularization (Koulu et al, 2004).…”

Leu7Pro polymorphism of PreproNPY associated with an increased risk for type II diabetes in middle-aged subjects

“…The results are in accordance with a recent report in Swedish men (Nordman et al, 2005) although in the present study the association was positive in both sexes. PreproNPY Leu7Pro polymorphism has been linked to accelerated atherosclerosis (Niskanen et al, 2000a) and progression of diabetic retinopathy (Niskanen et al, 2000b;Koulu et al, 2004) in type II diabetic subjects. Some studies have also related the Leu7Pro polymorphism with decreased insulin secretion (Jaakkola et al, 2005) and lower free fatty acid levels both in the fasting state and during the hyperinsulinemic clamp (Pihlajamäki et al, 2003).…”

“…NPY is, therefore, a good candidate gene for type II diabetes. The functional leucine 7 to proline (Leu7Pro) polymorphism in the signal peptide of NPY has been earlier associated with plasma NPY levels (Kallio et al, 2001(Kallio et al, , 2003, insulin metabolism (Kallio et al, 2003;Jaakkola et al, 2005), type II diabetes (Nordman et al, 2005) and its complications (Niskanen et al, 2000a, b;Koulu et al, 2004). The results have been, however, contradictory, and the mechanisms behind these associations largely unknown.…”

“…A commercial RIA kit recognizing both acylated and de-acylated ghrelin was used (Phoenix Pharmaceuticals Inc., Belmont, CA, USA). The routine clinical laboratory tests were carried out in the Central Laboratory of the Oulu University Hospital.Genotyping of the Leu7Pro polymorphism was performed as described earlier (Koulu et al, 2004). …”