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Title: Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro
Authors: Martins, João 
Elvas, Filipe 
Brudzewsky, Dan
Martins, Tânia 
Kolomiets, Bogdan
Tralhão, Pedro 
Gøtzsche, Casper R.
Cavadas, Cláudia 
Castelo-Branco, Miguel 
Woldbye, David P. D. 
Picaud, Serge
Santiago, Ana R. 
Keywords: calcium imaging; electrophysiology; neuromodulation; neuropeptide y; retinal explants; retinal ganglion cells
Issue Date: 2015
Publisher: SAGE Publications Inc.
Project: This work was supported by Fundac¸a˜o para a Cieˆncia e a Tecnologia, Portugal [PTDC/SAU-NEU/099075/2008, PTDC/NEU-OSD/1113/ 2012, PEst-C/SAU/UI3282/2011-2013, PEst-C/SAU/LA0001/ 2011-2013, UID/NEU/04539/2013, SFRH/BD/44817/2008], COMPETE/FEDER, and AIBILI. 
Serial title, monograph or event: ASN Neuro
Volume: 7
Issue: 4
Abstract: Neuropeptide Y (NPY) is expressed in mammalian retina but the location and potential modulatory effects of NPY receptor activation remain largely unknown. Retinal ganglion cell (RGC) death is a hallmark of several retinal degenerative diseases, particularly glaucoma. Using purified RGCs and ex vivo rat retinal preparations, we have measured RGC intracellular free calcium concentration ([Ca2+]i) and RGC spiking activity, respectively. We found that NPY attenuated the increase in the [Ca2+]i triggered by glutamate mainly via Y1 receptor activation. Moreover, (Leu31, Pro34)-NPY, a Y1/Y5 receptor agonist, increased the initial burst response of OFF-type RGCs, although no effect was observed on RGC spontaneous spiking activity. The Y1 receptor activation was also able to directly modulate RGC responses by attenuating the NMDA-induced increase in RGC spiking activity. These results suggest that Y1 receptor activation, at the level of inner or outer plexiform layers, leads to modulation of RGC receptive field properties. Using in vitro cultures of rat retinal explants exposed to NMDA, we found that NPY pretreatment prevented NMDA-induced cell death. However, in an animal model of retinal ischemia-reperfusion injury, pretreatment with NPY or (Leu31, Pro34)-NPY was not able to prevent apoptosis or rescue RGCs. In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs. However, further studies are needed to evaluate whether NPY neuroprotective actions detected in retinal explants can be translated into animal models of retinal degenerative diseases.
ISSN: 1759-0914
DOI: 10.1177/1759091415598292
Rights: openAccess
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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