Abstract
Purpose: :
To promote the injured optic nerve regeneration effectively in the adult mammalian , transplantation of Schwann cells (SCs) in an artificial grafts combining with transferring ciliary neurotrophic factor (CNTF) gene to retinal ganglion cells (RGCs) was tried.
Methods: :
To provide a suitable axonal growth environment, the tissue engineering nerve conduct consisting of SCs cultured in poly-lacticco-glycolic acid (PLGA) conduct was constructed and transplanted to the transected optic nerve stump in adult rats. Meanwhile, transferring CNTF gene into RGCs in vivo by electroporation was used to increase the injured RGCs survival and growth capability. Besides that, SCs was gene-modified in vitro by electroportation to increase their neurotrophic effect. After 4 weeks of transplantation, the effect of axonal regeneration was evaluated by DiI labeling and GAP43 staining of graft sections.
Results: :
By electroporation, CNTF gene was transferred to SCs effectively in vitro which was proven by RT-PCR and immunocytochemistry. The tissue engineering nerve conduct was good biocompatible and held abundant of SCs. Transplantation of CNTF gene modified SCs grafts promoted more axons to regenerate than SC grafts. And With the combinational therapy of transferring CNTF into RGCs in vivo by electroporation, transplantation of CNTF gene modified SCs grafts can reach the best effect.
Conclusions: :
The combinational use of genetically modified tissue engineering nerve conduct to bridge tissue defects and transferring neurotrophic factor gene to RGCs to enhance its intrinsic survival and regenerative capacity may provide new therapeutic strategies for the treatment of optic nerve injuries.
Keywords: optic nerve • transplantation • gene transfer/gene therapy