Extracellular ADP regulates lesion-induced cell proliferation and death in the zebrafish retina

ARIADNA BATTISTA; PAULA FAILLACE

Conferencia; 3dr Latin American Stem Cell Network Symposium; 2011

Persistent neurogenesis in the adult teleost fish has been a valuable tool to describe mechanisms involved in cell proliferation and differentiation. Damage of the mature retina activates tissue regeneration from intrinsic germinal cells. The aim of this study was to investigate the role of extracellular nucleotides on retinal regeneration. Zebrafish were lesioned by intravitreal injections of ouabain. Then, apyrase (enzyme that hydrolyses extracellular nucleotides) or different antagonists of purinergic receptors were injected daily for 6 days in the ouabain-treated eyes. On day 7 cell proliferation or death were determined. We observed that treatment with MRS2179, an antagonist of the ADP-activated P2Y1 receptor, completely blocked lesion-induced increases in cell division. In contrast, cell proliferation was not affected by blocking ADP-activated P2Y12, 13 receptors. Likewise, the injection of an antagonist of adenosine P1 receptors or a mixture of antagonists for ATP-activated P2Y11 or P2X1, 2, 3 receptors did not modify lesion-induced cell division. Additionally, extracellular nucleotides hydrolysis by treatment with apyrase significantly increased cell death in injured retinas. This effect was partially reproduced by blocking P2Y1 receptors. The present study demonstrates a crucial role for extracellular ADP in the repair of retina following injury via P2Y1 receptor.