Extracellular ADP regulates lesion-induced in vivo cell proliferation and death in the zebrafish retina.
Regeneration and growth that occur in the adult teleost retina by neurogenesis have been helpful in identifying molecular and cellular mechanisms underlying cell proliferation and differentiation. In this report, we demonstrate that endogenous purinergic signals regulate cell proliferation induced by a cytotoxic injury of the adult zebrafish retina which mainly damages inner retinal layers. Particularly, we found that ADP but not ATP or adenosine significantly enhanced cell division as assessed by 5-bromo-2'-deoxyuridine incorporation following injury, during the degenerative and proliferative phase of the regeneration process. This effect of ADP occurs via P2Y1 metabotropic receptors as shown by intra-ocular injection of selective antagonists. Additionally, we describe a role for purinergic signals in regulating cell death induced by injury. Scavenging of extracellular nucleotides significantly increased cell death principally seen in the inner retinal layers. This effect is partially reproduced by blocking P2Y1 receptors suggesting a neuroprotective function for ADP, which is derived from extracellular ATP probably released by dying cells as a consequence of the ouabain treatment. This study demonstrates a crucial role for ADP as a paracrine signal in the repair of retinal tissue following injury.
Battista
Ariadna G
AG
Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
Ricatti
María Jimena
MJ
Pafundo
Diego E
DE
Gautier
Marien A
MA
Faillace
María Paula
MP
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000963:Antimetabolites / Q000633:toxicity; D001973:Bromodeoxyuridine / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006868:Hydrolysis; D010042:Ouabain / Q000494:pharmacology; D019899:Paracrine Communication / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D015027:Zebrafish
D000963:Antimetabolites; D004791:Enzyme Inhibitors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D010042:Ouabain; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D001973:Bromodeoxyuridine; D000241:Adenosine