Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro

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João Martins, Filipe Elvas, Dan Brudzewsky, Tânia Martins, Bogdan Kolomiets, Pedro Tralhão, Casper R Gøtzsche, Cláudia Cavadas, Miguel Castelo-Branco, David P D Woldbye, Serge Picaud, Ana R Santiago, António F Ambrósio

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.

Original languageEnglish
JournalA S N Neuro
Volume7
Issue number4
Pages (from-to)1-21
Number of pages21
ISSN1759-0914
DOIs
Publication statusPublished - 2015

    Research areas

  • Animals, Animals, Newborn, Calcium, Cells, Cultured, Disease Models, Animal, Electroretinography, Gene Expression Regulation, Guanosine 5'-O-(3-Thiotriphosphate), In Situ Nick-End Labeling, Male, Neuropeptide Y, Peptide Fragments, Protein Binding, RNA, Messenger, Rats, Rats, Long-Evans, Rats, Wistar, Receptors, Neuropeptide Y, Retinal Diseases, Retinal Ganglion Cells, Sulfur Isotopes, Transcription Factor Brn-3A

ID: 161555985