Regeneration of zebrafish retina depends on the expression and activity of purinergic signaling molecules.

MARIA PAULA FAILLACE

Rosario

Congreso; SECOND MEETING OF LAZEN; 2012

Regeneration of zebrafish retina depends on the expression and activity of purinergic signaling molecules Maria Paula Faillace Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) - CONICET. Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Email: pfaillace@qb.ffyb.uba.ar   The adult retina of zebrafish exhibits cell regeneration and growth that occur during the animal´s life. This experimental model has helped to identify molecules and cellular mechanisms controlling cell proliferation and differentiation. On the other hand, cell extrinsic purinergic signals, which are composed by extracellular nucleotides/nucleosides, their purinergic or P receptors, and ectonucleoside tri-phosphate diphosphohydrolases (NTPDases), are essential for regulating cell proliferative activity and getting an adequate number of cells in the vertebrate nervous system development. It has also been demonstrated that purinergic signals have a central role in the genesis of the eye and retina in Xenopus laevis embryo. The aim of our studies has been to investigate the role of purinergic signals on adult retinal regeneration following cytotoxic injuries that provoke either partial or global cell death. To this end, we determined whether injured retinal cells were able to proliferate in the absence or presence of purinergic signaling molecules. We also examined if the injury provoked changes in the expression of purinergic receptors and NTPDases, which regulate extracellular nucleotide concentration. We have found that purinergic signals control progenitor cell proliferation for retinal regeneration in the adult zebrafish, regardless whether the injury involves only inner layers or the whole retina. Moreover, the activity of NTPDases is essential to increase cell proliferation. In addition, ADP-activated purinergic receptors P2Y1 are key regulators of cell cycle timing during regeneration in the neurogenic ciliary marginal zone as well as in mature layers. Furthermore, we first described several purinergic receptors P2 expressed by adult zebrafish retinas at the transcriptional level. A global damage of the adult zebrafish retina caused an increase and modified distribution of P2Y1 plasma membrane receptors, which are also likely expressed by proliferative cells suggesting a direct regulation of their mitotic activity. Furthermore, NTPDases 1, 2 and 3 mRNA levels were also enhanced during degenerative and proliferative phases. Additionally, extracellular nucleotides scavenging by treatment with apyrase significantly increased cell death in injured retinas. This effect was partially reproduced by blocking P2Y1 receptors. In sum, cell extrinsic nucleotides are necessary to control cell-cycle activity to enhance progenitor cell proliferation during retinal repair, regardless the magnitude of the injury. Purinergic signals appear to be also very important to limit cell death following injury and during the regeneration process. Grant sponsors: PIP 0169 CONICET 2009-2011 - UBACYT 0823 2011-1014, Universidad de Buenos Aires, Argentina.