title: Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro.
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.
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal.
authors: João
authors: J
authors: Martins
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal AIBILI, 3000-548 Coimbra, Portugal.
authors: Filipe
authors: F
authors: Elvas
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal AIBILI, 3000-548 Coimbra, Portugal.
authors: Dan
authors: D
authors: Brudzewsky
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal AIBILI, 3000-548 Coimbra, Portugal.
authors: Tânia
authors: T
authors: Martins
authors: Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, UMR_S968, 75012 Paris, France.
authors: Bogdan
authors: B
authors: Kolomiets
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal.
authors: Pedro
authors: P
authors: Tralhão
authors: Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors: Casper R
authors: CR
authors: Gøtzsche
authors: CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
authors: Cláudia
authors: C
authors: Cavadas
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal.
authors: Miguel
authors: M
authors: Castelo-Branco
authors: Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors: David P D
authors: DP
authors: Woldbye
authors: Sorbonne Universités, UPMC Univ Paris 06, Institut de la Vision, UMR_S968, 75012 Paris, France.
authors: Serge
authors: S
authors: Picaud
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal AIBILI, 3000-548 Coimbra, Portugal Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
authors: Ana R
authors: AR
authors: Santiago
authors: Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal CNC.IBILI, University of Coimbra, 3004-548 Coimbra, Portugal AIBILI, 3000-548 Coimbra, Portugal Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal afambrosio@fmed.uc.pt.
authors: António F
authors: AF
authors: Ambrósio
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004596:Electroretinography; D005786:Gene Expression Regulation / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D020287:In Situ Nick-End Labeling; D008297:Male; D009478:Neuropeptide Y / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012164:Retinal Diseases / Q000473:pathology / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*; D013460:Sulfur Isotopes / Q000493:pharmacokinetics; D050819:Transcription Factor Brn-3A / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D010446:Peptide Fragments; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D013460:Sulfur Isotopes; D050819:Transcription Factor Brn-3A; C062924:neuropeptide Y (13-36); D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002118:Calcium
keywords: calcium imaging; electrophysiology; neuromodulation; neuropeptide y; retinal explants; retinal ganglion cells