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.

Progression of retinal nerve fibre layer damage in betaxolol- and timolol-treated glaucoma patients.

PURPOSE: It has been suggested that there are differences between selective and non-selective beta-blocking agents in their ability to protect glaucomatous eyes. The purpose of this study was to follow glaucoma patients treated with either betaxolol 0.5% or timolol 0.25% ophthalmic solutions and to compare the rate and degree of progression in retinal nerve fibre layer (RNFL) defects between the groups. METHODS: A total of 64 patients were prospectively recruited in a double-masked study and randomly divided into two treatment groups. Retinal nerve fibre layer photographs were analysed. The incidence and total amount of progression in each group were recorded. The rate of impairment was demonstrated using Kaplan Meier survival curves. RESULTS: The analysis included 27 patients treated with betaxolol and 28 patients treated with timolol. Of these, 30% of betaxolol-treated patients and 46% of timolol-treated patients had RNFL damage progression (p = 0.20). The total amount or rate of progression did not differ significantly between the two groups. There was no significant difference in intraocular pressure (IOP) levels between the groups (p = 0.68) during follow-up. The degree of RNFL deterioration did not correlate to the amount of IOP reduction. CONCLUSION: The group treated with betaxolol 0.5% and the group treated with timolol 0.25% did not differ significantly in RNFL damage progression.