Retinal ganglion cells regenerating through the peripheral nerve graft retain their electroretinographic responses and mediate light-induced behavior

Abstract

To assess the light-induced electrical activity of rodent retinal ganglion cells (RGCs) regenerating into a peripheral nerve (PN) graft we used non-invasive recording of electroretinographic responses to the contrast-reversal of sinusoidal gratings (p-ERG). On comparing the retinas that received a PN graft and retinas with only optic nerve (ON) transection, p-ERG responses were present in grafted retinas as late as 20 months after the surgery while they completely disappeared in non-transplanted controls within 4 months of ON transection. Next, the ability of regenerating RGCs to form functional connections with their targets in the superior colliculus (SC) was tested by a light-escape task. While the bilaterally blinded animals did not improve during the test, unilaterally grafted animals (with the contralateral eye blinded) reached 26% success in the last quartile of the light-escape task. This performance was significantly better than that of blind animals (ANOVA and Student–Newman–Keuls test; p<0.05), but did not reach the level of intact rats (87%). The transplanted rats, therefore, were capable of light perception, but at a sub-normal ability. In addition, we were also able to correlate the amplitude of the p-ERG response with the visual behavioral performance for each transplanted animal. This finding indicates that there is a direct link between the RGC electrophysiological activity and the functional capacity of the regenerated visual pathway. In conclusion, the above results indicate that (a) PN grafts help to preserve the normal electroretinographic activity of injured and regenerating RGCs (b) the regenerated visual pathway is functional and capable of mediating simple visual behavior and that (c) there is a correlation between the light-evoked RGC electrical activity and visual behavior and, finally, that (d) the effect of PN graft on the electrophysiological and functional restoration of the visual pathway is long-lasting or even permanent.