Effects Of Inosine And Olfactory Ensheathing Cells On Neuronal Survival And Axonal Regeneration Of Axotomized Retinal Ganglion Cells In Adult Rats

Optic nerve and retina are derivatives of CNS. Optic nerve is composed of axonal of RGCs. Many regeneration studies have been carried out using the retina and optic nerve as a model system because the somata and myelinated axons of OECs can be manipulated separately and the retina can be studied as a flat-mounted preparation which facilitates the analysis of the RGCs in the entire retina. Damage to the central nervous system (CNS) is always followed by an irreversible axon degeneration of injured neurons. A wide variety of attempts have been made to enhance neuronal survival and axonal regeneration of axotomized neurons.Inosine, one of the catabolic products of purine nucleotide, has long been clinically used to supplementally treat a variety of diseases due to its involvement in energy synthesis. Recently, it has been reported that inosine can induce neuron of CNS to extend axons in vivo and vitro. In the first part of this study, we investigated the in vivo effects of inosine on the axon regeneration ofaxotomized RGCs in adult rats, using the model of peripheral nerve (PN) grafting onto the ocular stump of the transected optic nerve. Treatment with inosine induced a significant increase (62%) in the number of FluroGold -labeled RGCs regrowing their axons into the PN graft, when compared with the control animals. Our results showed that inosine could enhance the regeneration of axotomized RGCs in adult rats.OECs are glial cell and located in the CNS. On one hand, OECs can produce a variety of growth factors and adhesion molecules known to be involved in neuronal survival and axonal elongation. On the other hand, OECs transplanted into the adult CNS are able to integrate successfully within the host parenchyma and to migrate with the growing axons towards specific targets. Transplantation of OECs into the spinal cord parenchyma has been successfully used to enhance the regrowth of injured spinal nerve fibers in previous studies. In the second part, we investigated the in vivo effects of OECs on neuronal survival and axonal regeneration of axotomized RGCs in adult rats. In the survival studies, transplanted OECs significantly augmented RGCs survival 7 days postaxotomy. However, no same result was found 14 days postaxotomy. In the regeneration studies, the numbers of RGCs regrowing their axons into the PN graft 4 weeks after grafting were no significantly different between the experimental animals and the control animals. Our results showed that OECs promoted RGCs survival 7 days after postaxotomy. However, we didn't find that OECs promote regeneration of axotomized RGCs.