Skip to main content

Advertisement

SpringerLink
Log in

P2Y12 but not P2Y13 Purinergic Receptor Controls Postnatal Rat Retinogenesis In Vivo

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Adenine nucleotides through P2Y1 receptor stimulation are known to control retinal progenitor cell (RPC) proliferation by modulating expression of the p57KIP2, a cell cycle regulator. However, the role of Gi protein-coupled P2Y12 and P2Y13 receptors also activated by adenine nucleotides in RPC proliferation is still unknown. Gene expression of the purinergic P2Y12 subtype was detected in rat retina during early postnatal days (P0 to P5), while expression levels of P2Y13 were low. Immunohistochemistry assays performed with rat retina on P3 revealed P2Y12 receptor expression in both Ki-67-positive cells in the neuroblastic layer and Ki-67-negative cells in the ganglion cell layer and inner nuclear layer. Nonetheless, P2Y13 receptor expression could not be detected in any stratum of rat retina. Intravitreal injection of PSB 0739 or clopidogrel, both selective P2Y12 receptor antagonists, increased by 20 and 15%, respectively, the number of Ki-67-positive cells following 24 h of exposure. Moreover, the P2Y12 receptor inhibition increased cyclin D1 and decreased p57KIP2 expression. However, there were no changes in the S phase of the cell cycle (BrdU-positive cells) or in mitosis (phospho-histone-H3-positive cells). Interestingly, an increase in the number of cyclin D1/TUNEL-positive cells after treatment with PSB 0739 was observed. These data suggest that activation of P2Y12 receptors is required for the successful exit of RPCs from cell cycle in the postnatal rat retina.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Brzezinski JA, Reh TA (2015) Photoreceptor cell fate specification in vertebrates. Development 142:3263–3273. https://doi.org/10.1242/dev.127043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fan W, Li X, Yao H et al (2016) Neural differentiation and synaptogenesis in retinal development. Neural Regen Res 11:312. https://doi.org/10.4103/1673-5374.177743

    Article  PubMed  PubMed Central  Google Scholar 

  3. Centanin L, Wittbrodt J (2014) Retinal neurogenesis. Development 141:241–244. https://doi.org/10.1242/dev.083642

    Article  CAS  PubMed  Google Scholar 

  4. Reese BE (2011) Development of the retina and optic pathway. Vis Res 51:613–632. https://doi.org/10.1016/j.visres.2010.07.010

    Article  PubMed  Google Scholar 

  5. Masland RH (2012) The Neuronal Organization of the Retina. Neuron 76:266–280. https://doi.org/10.1016/j.neuron.2012.10.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cepko C (2014) Intrinsically different retinal progenitor cells produce specific types of progeny. Nat Rev Neurosci 15:615–627. https://doi.org/10.1038/nrn3767

    Article  CAS  PubMed  Google Scholar 

  7. Barton A, Fendrik AJ (2015) Retinogenesis: stochasticity and the competency model. J Theor Biol 373:73–81. https://doi.org/10.1016/j.jtbi.2015.03.015

    Article  CAS  PubMed  Google Scholar 

  8. Bassett E, Wallace V (2012) Cell fate determination in the vertebrate retina. Trends Neurosci 35:565–573. https://doi.org/10.1016/j.tins.2012.05.004

    Article  CAS  PubMed  Google Scholar 

  9. Ajioka I (2014) Coordination of proliferation and neuronal differentiation by the retinoblastoma protein family. Develop Growth Differ 56:324–334. https://doi.org/10.1111/dgd.12127

    Article  CAS  Google Scholar 

  10. Jin K (2017) Transitional progenitors during vertebrate retinogenesis. Mol Neurobiol 54:3565–3576. https://doi.org/10.1007/s12035-016-9899-x

    Article  CAS  PubMed  Google Scholar 

  11. Donovan SL, Dyer M (2005) Regulation of proliferation during central nervous system development. Semin Cell Dev Biol 16:407–421. https://doi.org/10.1016/j.semcdb.2005.02.012

    Article  CAS  PubMed  Google Scholar 

  12. Davis DM, Dyer MA (2010) Retinal progenitor cells, differentiation, and barriers to cell cycle reentry. Curr Top Dev Biol. https://doi.org/10.1016/B978-0-12-385044-7.00006-0

    Google Scholar 

  13. Harashima H, Dissmeyer N, Schnittger A (2013) Cell cycle control across the eukaryotic kingdom. Trends Cell Biol 23:345–356. https://doi.org/10.1016/j.tcb.2013.03.002

    Article  CAS  PubMed  Google Scholar 

  14. Frade JM, Ovejero-Benito MC (2015) Neuronal cell cycle: the neuron itself and its circumstances. Cell Cycle 14:712–720. https://doi.org/10.1080/15384101.2015.1004937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Swaffer MP, Jones AW, Flynn HR et al (2016) CDK substrate phosphorylation and ordering the cell cycle. Cell 167:1750–1761.e16. https://doi.org/10.1016/j.cell.2016.11.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT et al (1995) Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 82:621–630

    Article  CAS  Google Scholar 

  17. Fantl V, Stamp G, Andrews A, Rosewell I, Dickson C (1995) Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev 9:2364–2372

    Article  CAS  Google Scholar 

  18. Das G, Clark AM, Levine EM (2012) Cyclin D1 inactivation extends proliferation and alters histogenesis in the postnatal mouse retina. Dev Dyn 241:941–952. https://doi.org/10.1002/dvdy.23782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bertoli C, Skotheim JM, de Bruin RM (2013) Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol 14:518–528. https://doi.org/10.1038/nrm3629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sheppard KE, McArthur GA (2013) The cell-cycle regulator CDK4: an emerging therapeutic target in melanoma. Clin Cancer Res 19:5320–5328. https://doi.org/10.1158/1078-0432.CCR-13-0259

    Article  CAS  PubMed  Google Scholar 

  21. Westendorp B, Mokry M, Groot Koerkamp MJ et al (2012) E2F7 represses a network of oscillating cell cycle genes to control S-phase progression. Nucleic Acids Res 40:3511–3523. https://doi.org/10.1093/nar/gkr1203

    Article  CAS  PubMed  Google Scholar 

  22. Fisher RP (2016) Getting to S: CDK functions and targets on the path to cell-cycle commitment. F1000Research 5:2374. https://doi.org/10.12688/f1000research.9463.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lim S, Kaldis P (2013) Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development 140:3079–3093. https://doi.org/10.1242/dev.091744

    Article  CAS  PubMed  Google Scholar 

  24. Newman E (2001) Propagation of intercellular calcium waves in retinal astrocytes and Müller cells. J Neurosci 21:2215–2223

    Article  CAS  Google Scholar 

  25. Besson A, Dowdy SF, Roberts JM (2008) CDK inhibitors: cell cycle regulators and beyond. Dev Cell 14:159–169. https://doi.org/10.1016/j.devcel.2008.01.013

    Article  CAS  PubMed  Google Scholar 

  26. Yao G Modelling mammalian cellular quiescence. https://doi.org/10.1098/rsfs.2013.0074

    Article  Google Scholar 

  27. Johnson A, Skotheim JM (2013) Start and the restriction point. Curr Opin Cell Biol 25:717–723. https://doi.org/10.1016/j.ceb.2013.07.010

    Article  CAS  PubMed  Google Scholar 

  28. Praetorius H, Leipziger J (2009) ATP release from non-excitable cells. Purinergic Signal 5:433–446. https://doi.org/10.1007/s11302-009-9146-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Deng C, Ceruti S, Jaber M et al (2015) Vesicular expression and release of ATP from dopaminergic neurons of the mouse retina and midbrain. https://doi.org/10.3389/fncel.2015.00389

  30. Dahl G (2015) ATP release through pannexon channels. Philos Trans R Soc Lond Ser B Biol Sci 370:20140191. https://doi.org/10.1098/rstb.2014.0191

    Article  CAS  Google Scholar 

  31. Pearson R, Dale N, Llaudet E, Mobbs P (2005) ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation. Neuron 46:731–744. https://doi.org/10.1016/j.neuron.2005.04.024

    Article  CAS  PubMed  Google Scholar 

  32. Zimmermann H, Zebisch M, Sträter N (2012) Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal 8:437–502. https://doi.org/10.1007/s11302-012-9309-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yegutkin GG (2014) Enzymes involved in metabolism of extracellular nucleotides and nucleosides: functional implications and measurement of activities. Crit Rev Biochem Mol Biol 49:473–497. https://doi.org/10.3109/10409238.2014.953627

    Article  CAS  PubMed  Google Scholar 

  34. Burnstock G (2016) An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration. Neuropharmacology 104:4–17. https://doi.org/10.1016/j.neuropharm.2015.05.031

    Article  CAS  PubMed  Google Scholar 

  35. Oliveira Á, Illes P, Ulrich H (2015) Purinergic receptors in embryonic and adult neurogenesis. Neuropharmacology 104:272–281. https://doi.org/10.1016/j.neuropharm.2015.10.008

    Article  CAS  PubMed  Google Scholar 

  36. Kaczmarek-Hájek K, Lörinczi E, Hausmann R, Nicke A (2012) Molecular and functional properties of P2X receptors—recent progress and persisting challenges. Purinergic Signal 8:375–417. https://doi.org/10.1007/s11302-012-9314-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. North RA (2016) P2X receptors. Philos Trans R Soc B Biol Sci 371:20150427. https://doi.org/10.1098/rstb.2015.0427

    Article  CAS  Google Scholar 

  38. Jacobson K, Balasubramanian R, Deflorian F, Gao ZG (2012) G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions. Purinergic Signal 8:419–436. https://doi.org/10.1007/s11302-012-9294-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. von Kügelgen I, Hoffmann K (2015) Pharmacology and structure of P2Y receptors. Neuropharmacology 104:50–61. https://doi.org/10.1016/j.neuropharm.2015.10.030

    Article  CAS  Google Scholar 

  40. Liu X, Hashimoto-Torii K, Torii M, Haydar TF, Rakic P (2008) The role of ATP signaling in the migration of intermediate neuronal progenitors to the neocortical subventricular zone. Proc Natl Acad Sci U S A 105:11802–11807. https://doi.org/10.1073/pnas.0805180105

    Article  PubMed  PubMed Central  Google Scholar 

  41. Siow NL, Choi RCY, Xie HQ, Kong LW, Chu GKY, Chan GKL, Simon J, Barnard EA et al (2010) ATP induces synaptic gene expressions in cortical neurons: transduction and transcription control via P2Y1 receptors. Mol Pharmacol 78:1059–1071. https://doi.org/10.1124/mol.110.066506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. del Puerto A, Diaz-Hernandez J-I, Tapia M, Gomez-Villafuertes R, Benitez MJ, Zhang J, Miras-Portugal MT, Wandosell F et al (2012) Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation. J Cell Sci 125:176–188. https://doi.org/10.1242/jcs.091736

    Article  CAS  PubMed  Google Scholar 

  43. Heine C, Sygnecka K, Scherf N, Grohmann M, Bräsigk A, Franke H (2015) P2Y1 receptor mediated neuronal fibre outgrowth in organotypic brain slice co-cultures. Neuropharmacology 93:252–266. https://doi.org/10.1016/j.neuropharm.2015.02.001

    Article  CAS  PubMed  Google Scholar 

  44. Sanches G, de Alencar LS, Ventura ALM (2002) ATP induces proliferation of retinal cells in culture via activation of PKC and extracellular signal-regulated kinase cascade. Int J Dev Neurosci 20:21–27

    Article  CAS  Google Scholar 

  45. Sholl-Franco A, Fragel-Madeira L, Macama DCC et al (2010) ATP controls cell cycle and induces proliferation in the mouse developing retina. Int J Dev Neurosci 28:63–73. https://doi.org/10.1016/j.ijdevneu.2009.09.004

    Article  CAS  PubMed  Google Scholar 

  46. Pearson R, Catsicas M, Becker D, Mobbs P (2002) Purinergic and muscarinic modulation of the cell cycle and calcium signaling in the chick retinal ventricular zone. J Neurosci 22:7569–7579

    Article  CAS  Google Scholar 

  47. de Almeida-Pereira L, Magalhães CF, Repossi MG, Thorstenberg MLP, Sholl-Franco A, Coutinho-Silva R, Ventura ALM, Fragel-Madeira L (2016) Adenine nucleotides control proliferation in vivo of rat retinal progenitors by P2Y1 receptor. Mol Neurobiol 54:5142–5155. https://doi.org/10.1007/s12035-016-0059-0

    Article  CAS  PubMed  Google Scholar 

  48. Amadio S, Montilli C, Magliozzi R, Bernardi G, Reynolds R, Volonte C (2010) P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis. Cereb Cortex 20:1263–1273. https://doi.org/10.1093/cercor/bhp193

    Article  PubMed  Google Scholar 

  49. Sasaki Y, Hoshi M, Akazawa C, Nakamura Y, Tsuzuki H, Inoue K, Kohsaka S (2003) Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Glia 44:242–250. https://doi.org/10.1002/glia.10293

    Article  PubMed  Google Scholar 

  50. Pérez-Sen R, Queipo MJ, Morente V, Ortega F, Delicado EG, Miras-Portugal MT (2015) Neuroprotection mediated by P2Y13 nucleotide receptors in neurons. Comput Struct Biotechnol J 13:160–168. https://doi.org/10.1016/j.csbj.2015.02.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fragel-Madeira L, Meletti T, Mariante RM, Monteiro RQ, Einicker-Lamas M, Bernardo RR, Lopes AH, Linden R (2011) Platelet activating factor blocks interkinetic nuclear migration in retinal progenitors through an arrest of the cell cycle at the S/G2 transition. PLoS One 6:e16058. https://doi.org/10.1371/journal.pone.0016058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1016/0003-2697(76)90527-3

    Article  CAS  PubMed  Google Scholar 

  53. Battista AG, Ricatti MJ, Pafundo DE, Gautier MA, Faillace MP (2009) Extracellular ADP regulates lesion-induced in vivo cell proliferation and death in the zebrafish retina. J Neurochem 111:600–613. https://doi.org/10.1111/j.1471-4159.2009.06352.x

    Article  CAS  PubMed  Google Scholar 

  54. Jacques FJ, Silva TM, da Silva FE, Ornelas IM, Ventura ALM (2017) Nucleotide P2Y13-stimulated phosphorylation of CREB is required for ADP-induced proliferation of late developing retinal glial progenitors in culture. Cell Signal 35:95–106. https://doi.org/10.1016/j.cellsig.2017.03.019

    Article  CAS  PubMed  Google Scholar 

  55. Dyer M, Cepko CL (2001) p27Kip1 and p57Kip2 regulate proliferation in distinct retinal progenitor cell populations. J Neurosci 21:4259–4271

    Article  CAS  Google Scholar 

  56. Gampe K, Stefani J, Hammer K, Brendel P, Pötzsch A, Enikolopov G, Enjyoji K, Acker-Palmer A et al (2015) NTPDase2 and purinergic signaling control progenitor cell proliferation in neurogenic niches of the adult mouse brain. Stem Cells 33:253–264. https://doi.org/10.1002/stem.1846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Poche RA, Kwan KM, Raven MA, Furuta Y, Reese BE, Behringer RR (2007) Lim1 is essential for the correct laminar positioning of retinal horizontal cells. J Neurosci 27:14099–14107. https://doi.org/10.1523/JNEUROSCI.4046-07.2007

    Article  CAS  PubMed  Google Scholar 

  58. Chow RW, Almeida AD, Randlett O, Norden C, Harris WA (2015) Inhibitory neuron migration and IPL formation in the developing zebrafish retina. Development 142:2665–2677. https://doi.org/10.1242/dev.122473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Messina A, Bridi S, Bozza A, Bozzi Y, Baudet ML, Casarosa S (2016) Noggin 1 overexpression in retinal progenitors affects bipolar cell generation. Int J Dev Biol 60:151–157. https://doi.org/10.1387/ijdb.150402am

    Article  CAS  PubMed  Google Scholar 

  60. Levine EM, Green ES (2004) Cell-intrinsic regulators of proliferation in vertebrate retinal progenitors. Semin Cell Dev Biol 15:63–74. https://doi.org/10.1016/j.semcdb.2003.09.001

    Article  CAS  PubMed  Google Scholar 

  61. Rapaport DH, Wong LL, Wood ED, Yasumura D, LaVail MM (2004) Timing and topography of cell genesis in the rat retina. J Comp Neurol 474:304–324. https://doi.org/10.1002/cne.20134

    Article  PubMed  Google Scholar 

  62. Moheimani F, Jackson DE (2012) P2Y12 receptor: platelet thrombus formation and medical interventions. Int J Hematol 96:572–587. https://doi.org/10.1007/s12185-012-1188-5

    Article  PubMed  Google Scholar 

  63. Hu L, Chang L, Zhang Y, et al (2017) Platelets express activated P2Y12 receptor in patients with diabetes. Circulation CIRCULATIONAHA.116.026995. https://doi.org/10.1161/CIRCULATIONAHA.116.026995

    Article  CAS  Google Scholar 

  64. Liverani E, Rico MC, Tsygankov AY, Kilpatrick LE, Kunapuli SP (2016) P2Y12 receptor modulates sepsis-induced inflammation. Arterioscler Thromb Vasc Biol 36:961–971. https://doi.org/10.1161/ATVBAHA.116.307401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhang J, Li Z, Hu X, Su Q, He C, Liu J, Ren H, Qian M et al (2017) Knockout of P2Y 12 aggravates experimental autoimmune encephalomyelitis in mice via increasing of IL-23 production and Th17 cell differentiation by dendritic cells. Brain Behav Immun 62:245–255. https://doi.org/10.1016/j.bbi.2016.12.001

    Article  CAS  PubMed  Google Scholar 

  66. Irino Y, Nakamura Y, Inoue K, Kohsaka S, Ohsawa K (2008) Akt activation is involved in P2Y12 receptor-mediated chemotaxis of microglia. J Neurosci Res 86:1511–1519. https://doi.org/10.1002/jnr.21610

    Article  CAS  PubMed  Google Scholar 

  67. Mildner A, Huang H, Radke J, Stenzel W, Priller J (2017) P2Y 12 receptor is expressed on human microglia under physiological conditions throughout development and is sensitive to neuroinflammatory diseases. Glia 65:375–387. https://doi.org/10.1002/glia.23097

    Article  PubMed  Google Scholar 

  68. Sipe GO, Lowery RL, Tremblay M-È et al (2016) Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex. Nat Commun 7:10905. https://doi.org/10.1038/ncomms10905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kawaguchi A, Sato M, Kimura M, Ichinohe T, Tazaki M, Shibukawa Y (2015) Expression and function of purinergic P2Y12 receptors in rat trigeminal ganglion neurons. Neurosci Res 98:17–27. https://doi.org/10.1016/j.neures.2015.04.008

    Article  CAS  PubMed  Google Scholar 

  70. Del Puerto A, Wandosell F, Garrido JJ (2013) Neuronal and glial purinergic receptors functions in neuron development and brain disease. Front Cell Neurosci 7:197. https://doi.org/10.3389/fncel.2013.00197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Galli-Resta L, Novelli E, Viegi A (2002) Dynamic microtubule-dependent interactions position homotypic neurones in regular monolayered arrays during retinal development. Development 129:3803–3814

    CAS  PubMed  Google Scholar 

  72. Quintas C, Fraga S, Gonçalves J, Queiroz G (2011) Opposite modulation of astroglial proliferation by adenosine 5’-O-(2-thio)-diphosphate and 2-methylthioadenosine-5′-diphosphate: Mechanisms involved. Neuroscience 182:32–42. https://doi.org/10.1016/j.neuroscience.2011.03.009

    Article  CAS  PubMed  Google Scholar 

  73. Hardy AR, Jones ML, Mundell SJ, Poole AW (2004) Reciprocal cross-talk between P2Y 1 and P2Y 12 receptors at the level of calcium signaling in human platelets. Blood 104:1745–1752. https://doi.org/10.1182/blood-2004-02-0534.Supported

    Article  CAS  PubMed  Google Scholar 

  74. Krzeminski P, Misiewicz I, Pomorski P, Kasprzycka-Guttman T, Brańska J (2007) Mitochondrial localization of P2Y1, P2Y2 and P2Y12 receptors in rat astrocytes and glioma C6 cells. Brain Res Bull 71:587–592. https://doi.org/10.1016/j.brainresbull.2006.11.013

    Article  CAS  PubMed  Google Scholar 

  75. Mchonde GJ, Satoh Y, Yasuhira S, et al Intracellular calcium dynamics and expression of P2Y and IP3 receptors in a cycling G1-phase cell

  76. Dyer MA, Cepko CL (2000) p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina. Development 127:3593–3605

    CAS  PubMed  Google Scholar 

  77. Ochocinska MJ, Hitchcock PF (2009) NeuroD regulates proliferation of photoreceptor progenitors in the retina of the zebrafish. Mech Dev 126:128–141. https://doi.org/10.1016/j.mod.2008.11.009

    Article  CAS  PubMed  Google Scholar 

  78. Alexiades MR, Cepko C (1996) Quantitative analysis of proliferation and cell cycle length during development of the rat retina. Dev Dyn 205:293–307. https://doi.org/10.1002/(SICI)1097-0177(199603)205:3<293::AID-AJA9>3.0.CO;2-D

    Article  CAS  PubMed  Google Scholar 

  79. Skapek SX, Lin S-CJ, Jablonski MM, McKeller RN, Tan M, Hu N, Lee EYHP (2001) Persistent expression of cyclin D1 disrupts normal photoreceptor differentiation and retina development. Oncogene 20:6742–6751. https://doi.org/10.1038/sj.onc.1204876

    Article  CAS  PubMed  Google Scholar 

  80. Ma C, Papermaster D, Cepko CL (1998) A unique pattern of photoreceptor degeneration in cyclin D1 mutant mice. Proc Natl Acad Sci U S A 95:9938–9943

    Article  CAS  Google Scholar 

Download references

Funding

This study received grant support from the Brazilian funding agencies Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo Research Foundation, FAPESP Proj. Nr. 2012/50880-4), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ Proj. Nr.110.145/2014), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for fellowship support.

Author information

Authors and Affiliations

  1. Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil

    Luana de Almeida-Pereira, Marinna Garcia Repossi, Camila Feitosa Magalhães, Rafael de Freitas Azevedo, Ana Lúcia Marques Ventura & Lucianne Fragel-Madeira

  2. Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil

    Juliana da Cruz Corrêa-Velloso & Henning Ulrich

Authors
  1. Luana de Almeida-Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marinna Garcia Repossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Camila Feitosa Magalhães
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rafael de Freitas Azevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juliana da Cruz Corrêa-Velloso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Henning Ulrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ana Lúcia Marques Ventura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lucianne Fragel-Madeira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lucianne Fragel-Madeira.

Electronic supplementary material

Supplementary Figure 1

P2Y12 receptor was expressed in P2 rat retina. Projection of confocal optical sections showing that P2Y12 labeling was found in Ki-67 positive and negative cells in the NBL. The RPCs nuclei were stained with DAPI (blue), P2Y12 in red and Ki-67 in green. Scale bar = 50 μm. (GIF 395 kb)

High resolution image (TIFF 48887 kb)

Supplementary Figure 2

P2Y12 receptor blockage receptor in rat retina in vitro increased proliferation of RPC. Explants at P2 rat retina were treated with PSB 0739 at concentrations of 0.05, 0.1 and 1 μM for 24 h. Treatment at 1 μM concentration increased the number of Ki-67 positive cells relative to the control (Control = 6552 ± 185; 0.05 μM = 7506 ± 328.3; 0.1 μM = 7281 ± 370.2; 1 μM = 8384 ± 644). Data are mean values ± S.E.M. from three independent experiments. *p < 0.05 as compared to control. (GIF 11 kb)

High resolution image (TIFF 900 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Almeida-Pereira, L., Repossi, M.G., Magalhães, C.F. et al. P2Y12 but not P2Y13 Purinergic Receptor Controls Postnatal Rat Retinogenesis In Vivo. Mol Neurobiol 55, 8612–8624 (2018). https://doi.org/10.1007/s12035-018-1012-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-018-1012-1

Keywords

Search

Navigation