BDNF and EphA3 ectodomain stimulate retinal ganglion cell axon growth and guidance.

SPELZINI, GONZALO; TERUEL, LUISA R; MEDORI, MARA; SANCHEZ, VIVIANA; FIORE, LUCIANO; SCICOLONE, GABRIEL

Congreso; SAN 2020. XXXV Virtual Meeting; 2020

Sociedad Argentina de Investigacion en Neurociencias

BDNF and EphA3 ectodomain stimulate retinal ganglion cell axon growth and guidance. GONZALO SPELZINI*1,2; LUISA RENEE TERUEL1,2; MARA MEDORI1,2; VIVIANA SANCHEZ1,2; LUCIANO FIORE1,2; GABRIEL SCICOLONE1,2.1. CONICET ? Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencias ?Prof. E. De Robertis? (IBCN). Ciudad de Buenos Aires, Argentina.2, Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética. Ciudad de Buenos Aires, Argentina.We demonstrated that tectal EphA3 stimulates axon growth of nasal retinal ganglion cells (RGC) toward the caudal tectum preventing them from branching in the rostral tectum. BDNF stimulates RGC axon growth and branching. However its effect on RGC axon guidance is not clear and there is no evidence about the combinatorial effects of EphA3 ectodomain and BDNF.Our purpose was to study the individual and combinatorial effects of EphA3 and BDNF on RGC axon growth and guidance. We cultured chicken embryo nasal retinal explants and dissociated RGCs on poly-L-lysine/laminin and exposed them to control conditions, to EphA3 ectodomain (aggregated EphA3-Fc), to BDNF or to EphA3-Fc plus BDNF to evaluate their effects on axon growth and guidance. In order to evaluate the participation of gradients of BDNF and EphA3 on the axonal guidance of nasal RGCs, we developed a chemotaxis test using the Dunn´s chamber.The results showed that: EphA3-Fc and BDNF increase the length of nasal RGC axons and that nasal RGC axons change their directions of growth toward gradients of EphA3 and BDNF. Besides, EphA3-Fc and BDNF together present the highest effects in comparison to the effects produced by any of them alone. This demonstrates that BDNF and EphA3 not only stimulate RGC axon growth but their gradients also have chemoattractant effects on nasal RGC axons, suggesting that both of them present synergistic effects. UBACYT 0769.Key words: Axon guidance, Eph/ephrin, BDNF, retina.