ROLE OF THE PURINERGIC RECEPTOR P2X7 IN THE REGULATION OF THE PROLIFERATIVE, VASCULAR AND INFLAMMATORY RESPONSE IN THE INJURED RETINA OF ADULT ZEBRAFISH

MEDRANO, MATIAS PEDRO; FAILLACE, MARÍA PAULA

Congreso; Reunión Conjunta de Sociedades de BioCiencias 2017; 2017

Unlike mammals, zebrafish canregenerate retinal neurons to replace those lost by injury or disease. Müllerglia in mammals responds with hypertrophy and scarring. Injury-responsive Müllercells in zebrafish show limited gliosis and cell cycle reprogramming to repair theretina. The P2X7 purinergic receptor (P2RX7) has been involved in the genesisof retinopathies in rodents and humans. We characterized a hypoxia-like injuryby delivering CoCl2 intraocularly that virtually kills all photoreceptorsin the zebrafish retina. So we examined here the in vivo regenerative response of CoCl2-injured retinasin the presence or absence of a specific P2RX7 antagonist (A740003). Wequantified the number of proliferative progenitor and microglial cells. We labeledendothelial cells and assessed GFAP immunoreactivity. Quantitative mRNAexpression of different hypoxia-induced genes and cell proliferation-relatedgenes was also analyzed by RT-qPCR. Lesioned retinas treated with A740003showed a significant increase in the number of proliferative progenitorsincluding a larger number of dividing nuclei of the GFAP-positive Müller glia. Thenumber of microglial cells around vessels and proliferation-related gene expressionwere also significantly enhanced. Vascular endothelial growth factor and itsreceptor and Hypoxia-induced factor genes were differentially expressed in theantagonist-treated retinas. Likewise, apyrase-treated injured retinas exhibiteda larger number of proliferative cells while the number of apoptotic cellsincreased in all retinal layers and that of bipolar cells displayed asignificant decrease.The antagonist of P2X7R enhanced overall injuryseverity. Similar results were observed when extracellular nucleotides were eliminatedby an excess of intraocular apyrase. These findings suggest that the P2X7R playsa crucial neuroprotective role in the zebrafish retina since the selective blockadeof its activity had a deleterious impact on the injured tissue.