S-076 | Role of the Eph-ephrin System and Neurotrophic Factors in Cone Growth Morphology and Axon Guidance Dynamics of Retinal Ganglion Cells

Development
Author: Gonzalo Nicolás Spelzini | Email: gspelzini@fmed.uba.ar

Gonzalo Spelzini^1°2°, Mara Medori^1°2°, Sofía Martin Mena^1°2°,  Alejandro Scicolone^3°, Viviana Sanchez^1°2°, Luciano Fiore^1°2°, Gabriel Scicolone^1°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.
^3° Universidad de Buenos Aires, Facultad de Medicina, Departamento de Medicina interna. Ciudad de Buenos Aires, Argentina

Introduction: Tectal EphA3 stimulates axon growth of nasal retinal ganglion cells (RGCs)
towards the caudal tectum, inhibiting branching in the rostral tectum. GDNF and BDNF
stimulates RGC axon growth, though its effects on RGC growth cone morphology and guidance
are unclear. The combined effects of EphA3 with GDNF or BDNF on RGCs remain
unexplored.Objectives: This study examines the individual and combined effects of EphA3,
GDNF, and BDNF on RGC growth cone morphology and dynamics.Methods: Dissociated nasal
RGCs from chicken embryos were cultured and exposed to EphA3-Fc, GDNF, BDNF, or EphA3-Fc
combined with neurotrophic factors. Growth cone velocity and morphology were assessed.
Axonal guidance responses to gradients were tested using a chemotaxis assay with Dunn’s
chamber.Results: RGC axons showed directed growth towards EphA3, GDNF, and BDNF
gradients, with increased axon outgrowth velocities. EphA3-Fc combined with GDNF produced
the strongest effects. Growth cones showed consistent velocity variations along their paths,
with extended growth phases under combined GDNF and EphA3-Fc gradients, enhancing
overall growth cone advancement and reducing collapse. Combined BDNF and EphA3-Fc
gradients also increased growth phase velocities.Conclusion: GDNF, BDNF, and EphA3 promote
RGC axon outgrowth velocity and act as chemoattractants, with synergistic effects. These
findings highlight the impact of chemotactic cues on growth cone morphology and
movement.Support: UBACYT0197BA.