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

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.

Brain-derived neurotrophic factor and neurotrophin-4/5 stimulate growth of axonal branches from regenerating retinal ganglion cells.

To investigate the influences of growth factors on axonal regeneration in the mammalian CNS, we used intracellular tracers to quantitate the effects of brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-4/5, or NT-3 on individual retinal ganglion cell (RGC) axons in the retinas of adult rats after optic nerve transection. A single injection of BDNF or the prolonged administration of NT-4/5 by mini-pump increased axon branch median lengths by eightfold but had no effect on the number of branches formed by the RGC axons. NT-3 did not significantly influence axonal regrowth. These specific in vivo effects of BDNF and NT-4/5 on axonal regeneration from injured RGCs may be used to promote growth and expand the abnormally small terminal arbors observed when RGCs regrow into their CNS targets.

Effects of neurotrophins on the survival and regrowth of injured retinal neurons.

The focus of this short review is the role of certain neurotrophins and their receptors on the survival and regrowth of retinal ganglion cells (RGCs) whose axons are damaged in the optic nerve. Initial experiments in our laboratory documented patterns of RGC death after axotomy. Subsequent studies were designed to investigate the distribution of high-affinity neurotrophin receptors in neurons and glial cells of the retina and optic nerve. This information was used both in vitro and in vivo to study the effects of specific trophic molecules on the survival and regrowth of injured RGCs. During the course of experiments involving neurotrophin administration, an endogenous source of trophic support--independent of the exogenous administration of growth factors--was found within the eye. Several experiments were subsequently undertaken to define further this survival effect and determine its nature and source within the eye. Finally, anatomical techniques that help visualize fine axonal processes within the retina have provided insights into the specific effects of neurotrophins on the growth and branching of injured CNS axons.

IBM PC based visual evoked potential stimulator and averager.

Custom made hard and software enhancement of an IBM PC is described which makes it possible to: i) provide patterned visual stimulation by using the EGA or higher level display, ii) average recorded potentials and iii) monitor the experiment simultaneously. The description is illustrated by examples from a study of retinal evoked potentials in the rat.