Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro
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Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro. / 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; Ambrósio, António F.
In: A S N Neuro, Vol. 7, No. 4, 2015, p. 1-21.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro
AU - Martins, João
AU - Elvas, Filipe
AU - Brudzewsky, Dan
AU - Martins, Tânia
AU - Kolomiets, Bogdan
AU - Tralhão, Pedro
AU - Gøtzsche, Casper R
AU - Cavadas, Cláudia
AU - Castelo-Branco, Miguel
AU - Woldbye, David P D
AU - Picaud, Serge
AU - Santiago, Ana R
AU - Ambrósio, António F
N1 - © The Author(s) 2015.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Newborn
KW - Calcium
KW - Cells, Cultured
KW - Disease Models, Animal
KW - Electroretinography
KW - Gene Expression Regulation
KW - Guanosine 5'-O-(3-Thiotriphosphate)
KW - In Situ Nick-End Labeling
KW - Male
KW - Neuropeptide Y
KW - Peptide Fragments
KW - Protein Binding
KW - RNA, Messenger
KW - Rats
KW - Rats, Long-Evans
KW - Rats, Wistar
KW - Receptors, Neuropeptide Y
KW - Retinal Diseases
KW - Retinal Ganglion Cells
KW - Sulfur Isotopes
KW - Transcription Factor Brn-3A
U2 - 10.1177/1759091415598292
DO - 10.1177/1759091415598292
M3 - Journal article
C2 - 26311075
VL - 7
SP - 1
EP - 21
JO - A S N Neuro
JF - A S N Neuro
SN - 1759-0914
IS - 4
ER -
ID: 161555985