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

Intraorbital transection of the optic nerve always induces ultimate death ofretinal ganglion cells (RGCs) and consequently irreversible defects of visionfunction. Deprivation of target-derived neurotrophic factors has been thought tobe one of the major explanations for such RGCs death. Many strategiesincluding application of neurotrophic factors have been demonstrated to be ableto protect axotomized RGCs.Olfactory ensheathing cells (OECs), a sort of macroglial cells found in thenasal olfactory mucosa and olfactory bulb, can secrete neurotrophins such asnerve growth factor, brain-derived neurotrophic factor (BDNF) andneurotrophin-4/5(NT-4/5). Previous investigations also showed that conditionedmedium of adult rat OECs protected PC12cells from Zn+insult in vitro andtransplanted OECs in the partially injured spinal cord have a distant in vivoneuroprotective effect on descending cortical and brain stem neurons. However,no study has investigated the effects of transplanted OECs on RGCs survival although OECs have been shown to enhance axonal regeneration of axotomizedRGCs. Because the distance between the soma and axonal injury site of aneuron has a definite effect on the severity of neuronal response and apoptosis,more neurons die with a closer axonal injury. In the present study, wetransplanted OECs into the ocular stump of intraorbitally transected ON in adultrats to see whether OECs protect injured RGCs with a very close axonal injury.In the present study, the number of surviving RGCs increased at the7th dayafter OECs transplantation and a significantly promoted mRNA and proteinlevels of BDNF was observed simultaneously within the ocular ON stump andretina.Lithium has been used as a mood–stabilizing drug to treat bipolar mooddisorder for over half a century and remains one of the primary antidepressantdrugs. In recent years, a large number of studies, encompassing in vitro, in vivohave concluded that lithium is neuroprotcetive. Lithium protects neurons in theinjured central nervous system by increasing BDNF and cAMP responseelement binding protein in the brain. In our study, we not only use the lithium topromote the repair of the injured RGCs but also take advantage of thecharacteristics of the lithium to increase expression of BDNF in retina afterOECs transplantation.We combine lithium with transplantation of OECs to seewhether they protect injured RGCs at14days after optic nerve transaction. Theresult of experiment show that combiniation lithium with OECs has noneuroprotive effect on injured RGCs. However, lithium treatment was able topromote injured RGCs regrowing their axons into the PN graft.