Synergetic effects of ciliary neurotrophic factor and olfactory ensheathing cells on optic nerve reparation

Abstract

This study is to investigate the effect of the combination of the olfactory ensheathing cells (OEC) transplantation and intravitreous injection of ciliary neurotrophic factor (CNTF) on the retinal ganglia cells' (RGC) apoptosis and axonals' reparation and regeneration. In this study, the supraorbital margin exposure of the optic nerves was used to establish adult SD rats' optic nerve inhausted injury model as control group. Then the purified OECs were injected into the optic nerve sheaths, and CNTF was injected into the vitreous body simultaneously. The rats were divided into control group, CNTF group, OECs group, and OEC+CNTF combined group. At 4 weeks postoperatively, a cholera toxin B subunit (CTB) anterograde tracing technique and fluorescence (FG) biotinylated dextran amine (BDA) retrograde tracing technique were adopted to evaluate the survival of RGC and the regeneration of optic nerve axons. The number of survival neurons of the same vision field and the density of neurons were evaluated by analysis of variance. At the one and three quadrant distance between optic disc 2 mm spot, the number of the RGC in the control group was significantly (F = 633.38, P < 0.01) decreased compared with the normal group (46.00 ± 1.42, 34.80 ± 1.34, 25.00 ± 1.61, 15.40 ± 2.30). The survived RGC in OEC group was significantly more than that in CNTF group, while the combined treatment with CNTF and OEC had strongest repair effect. The neuron axon density showed a statistically significant difference in the average optical density value at distance between foramen opticum 2 mm spot (OEC+CNTF: 3.18 ± 0.26, OEC: 2.96 ± 0.28, CNTF: 2.83 ± 0.37, and control: 2.75 ± 0.12, respectively, F = 17.66, P < 0.01) . Optic nerves damage can be repaired and regenerated by the combined treatment with OEC and CNTF suggesting that CNTF and OEC have synergistic effect on the treatment of optic nerve injury and repair. Transplantation of OECs may genetically modify the secretion of human CNTF and promote optic nerve injury repair.