Glutamatergic control of cell growth in the zebrafish retina

CARLOS DAVID BRUQUE AND MP FAILLACE

Buenos Aires

Simposio; 2do SIMPOSIO FRANCO ARGENTINO DE NEUROCIENCIAS; 2012

LIA DEVENIR (LaNyN, IBCN and CGPhiMC (CNRS, Univ Lyon 1 , France)

Glutamatergic control of cell growth in the zebrafish retina Carlos Bruque1, Maria Paula Faillace1,2 1Departamento de Fisiología, Facultad de Medicina, UBA  2IQUIFIB-CONICET, Buenos Aires, Argentina   The retina of zebrafish grows throughout animal’s life from an intrinsic germinal region at the periphery of the retina called ciliary marginal zone (CMZ). This animal model allows studying cell proliferation and differentiation processes to generate new cell types of the adult retina. We have described variations in the number of cells in S-phase of the cell cycle during the light/dark photoperiod with a peak of cell proliferation observed at the middle of the light phase. On the other hand, glutamatergic transmission from photoreceptors to bipolar cells (BC) and from BC to ganglion cells (GC) mediates light processing and information transmission to the visual brain centers. We blocked the depolarization of ON BC, which are activated in response to light, through an agonist (L-AP4) of mGluR6 receptors, whose activation by glutamate hyperpolarizes ON BC. We also used an antagonist of AMPA receptors DNQX, to block excitatory synapses between photoreceptors and OFF BC and between BC and all GC (although part of the response is NMDA receptor-mediated). DNQX treatment significantly increased proliferating cell number (measured by BrdU incorporation for 4 h in the CMZ). Moreover, L-AP4 did not modify cell proliferative activity. However, AP5 (an antagonist of NMDA receptors) significantly decreased cell proliferation in the CMZ. Therefore, these results suggest a relevant role of glutamate (possibly in response to the light/dark cycle) in regulating mitotic activity and retinal growth in the adult zebrafish. Whether glutamate effect occurs directly on proliferating cells or throughout other extracellular signals is under investigation.