IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Purinergic signals control cell proliferation and death underlying retinal regeneration
Autor/es:
MARIA PAULA FAILLACE ; ARIADNA BATTISTA
Lugar:
Ouro Preto
Reunión:
Congreso; Third Meeting of the Brazilian Purines Club 2012, Purinergic Signaling: Biological and therapeutic implications.; 2012
Institución organizadora:
The Brazilian Purine Club
Resumen:
Cell extrinsic purinergic signals regulate lesion-induced cell proliferation and death in the adult zebrafish retina Maria Paula Faillace  (invited speaker in symposia) and Ariadna Battista. Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) - CONICET. Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.   Regeneration and growth that occur in the adult fish retina have helped to identify molecules and cellular mechanisms controlling cell proliferation and differentiation. It has been described that retinas cannot regenerate if photoreceptor cells remain undamaged. However, damage to the inner retinal cells can trigger retinal repair without disturbing photoreceptor cells. On the other hand, cell extrinsic purinergic signals are essential for regulating cell proliferative activity and getting an adequate number of cells in the vertebrate nervous system development, including a central role in the genesis of the eye and retina. 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 regenerate and proliferate in the absence or presence of purinergic signaling. We also examined if there was a change in the level and pattern of expression of purinergic receptors and ectonucleoside tri-phosphate diphosphohydrolases (NTPDases). 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 ciliary marginal zone and 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 causes 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, NTPDase1, 2 and 3 mRNA levels were also enhanced during degenerative and proliferative phases following injury. 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.