Purchase this article with an account.
Ana Santos-Carvalho, Antonio F. Ambrósio, Cláudia Cavadas; Neuropeptide Y Protects Retinal Neural Cells From Glutamate-induced Toxicity Through The Activation Of NPY Y5 Receptor. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6538.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to investigate the potential protective role of Neuropeptide Y against glutamate-induced toxicity in cultured rat retinal cells and identify the NPY receptors mediating the protective effect.
Rat retinal neural cell cultures were prepared from newborn Wistar rats (P3-P5). The expression and distribution of NPY Y5 receptors was assessed by T-PCR and immunocytochemistry. Cells were exposed to glutamate (500 µM) for 24h. Necrotic cell death was evaluated by propidium iodide (PI) assay and apoptotic cell death by TUNEL assay. The neuroprotective role of NPY Y5 receptor activation was studied using a receptor selective NPY Y5 agonist and antagonist.
NPY inhibited the glutamate necrotic and apoptotic cell death by 27.7±3,7% and 30.3%±3.8% respectively. By RT-PCR and immunocytochemistry, we observed that NPY Y5 receptor is present in all cell types present in retinal cultures: neurons, microglia and macroglia. The NPY Y5 receptor agonist [(NPY19-23(Gly1, Ser3, Gln4, Thr6, Ala31, Aib32,Gln34); 100 nM] inhibited the necrotic cell death (PI-positive cells) induced by exposure to glutamate by 27.0±4.4%, compared to glutamate alone. This protective effect was completely blocked by the NPY Y5 receptor antagonist (L-152,804; 1µM). This agonist also decreased 31.8±6.0% the number of TUNEL-positive cells induced by glutamate. Again, this effect was completely blocked by the Y5 receptor antagonist.
The NPY Y5 receptors are present in all cell types present in rat retinal cell cultures. Its activation protects retinal neural cells from both necrotic and apoptotic cell death induced by glutamate. Therefore, NPY Y5 receptor may be viewed as a potential therapeutic target for the treatment of retinal degenerative diseases, such as glaucoma.
This PDF is available to Subscribers Only