After a complete optic nerve section (ONS), retinal neurons may display retrograde transneuronal modifications in synaptic structure and function related to the retinal disconnection from the brain. The molecular and physiological basis of these changes is not yet fully understood. Immunoreactivity for calbindin was used to specifically immunolabel the horizontal cells (HC) in order to study any morphologic changes in the outer plexiform layer (OPL) after axotomy-induced degeneration of retinal ganglion cells (RGC) in the rabbit retina. Glutamate-gated conductance expressed by HC enzymatically dissociated from the rabbit retina were studied at 12 and 21 days after ONS by using the whole-cell voltage-clamp technique. The amplitudes of glutamate-induced currents on HC were significantly reduced 3 weeks after axotomy. However, no morphologic changes within the OPL were detected coincident with the progressive loss of glutamatergic responses; similarly, HC dissociated from the axotomized retinal tissue did not differ in morphology or appearance from control retinas. The main finding in this study is that the HC experiment a retrograde transneuronal down-regulation of their ionotropic glutamate-induced conductance following axotomy-induced degeneration of RGC.