Blockade of P2RX7 and extracellular nucleotide depletion enhanced injury severity and Müller glia-derived multipotent progenitor cell proliferation in the zebrafish retina

MARIA PAULA FAILLACE

Seminario; CLUB DE LA GLIA - SEMINAROS CIENTIFICOS; 2020

CLUB DE LA GLIA - AULA VIRTUAL ZOOM DE LA SOCIEDAD ARGENTINA DE INVESTIGACIONES EN NEUROCIENCIAS (SAN)

La charla dictada en español, se encuentra publicada en forma de un video en YOUTUBE CLUB DE LA GLIA. Unlike mammals,zebrafish can regenerate retinal neurons to replace those lost by injury ordisease. Müller glia in mammals responds with hypertrophy and scarring.Injury-responsive Müller cells in zebrafish show limited gliosis and cell cyclereprogramming to repair the retina. The P2X7 purinergic receptor (P2RX7) hasbeen involved in the genesis of retinopathies in rodents and humans.We characterized ahypoxia-like injury by delivering CoCl2 intraocularly thatvirtually kills all photoreceptors in the zebrafish retina. So we examined herethe invivo regenerativeresponse of CoCl2-injured retinas in the presence or absence ofpurinergic signalling and thespecific inhibition of ATP on P2RX7-mediated signalling. Apyrase-treatedinjured retinas exhibited a larger number of proliferative cells relative tosaline-treated injured retinas. Apoptotic cell number was increased inall retinal layers. Bipolar cells were more severely affected inapyrase-treated injured retinas. Vascular endothelial growth factor(VEGF), its receptors, hypoxia-induced and proliferation related genes weredifferentially expressed in the P2RX7 antagonist-treated retinas.Proliferative progenitors including GFAP-positive dividing Müller glia showed asignificant increase in A740003-treated injured retinas (Fig 5). The number ofmicroglial cells around the optic disc arteries and peripheral capillaries wasfurther enhanced when retinas were treated with A740003. Blockadeof P2RX7 enhanced overall injury severity and multipotent progenitor cell proliferation. Similar results wereobserved when extracellular nucleotides were eliminated by the invivo apyrase treatment. Thesefindings suggest that extracellular ATP acting via the P2RX7 plays a crucial neuroprotective role in thezebrafish.