Effects of immunosuppression on regrowth of adult rat retinal ganglion cell axons into peripheral nerve allografts.
Analysis of the effectiveness of allografts and immunosuppression in the repair of nerve defects in the adult peripheral nervous system (PNS) has a long experimental and clinical history. There is little information, however, on the use of allografts in peripheral nerve (PN) transplantation into the injured central nervous system (CNS). We assessed the ability of PN allografts (from Dark-Agouti rats) to support regeneration of adult rat retinal ganglion cell (RGC) axons in immunosuppressed host Lewis rats. PN allografts were sutured onto intraorbitally transected optic nerves. Three weeks after grafting, regenerating RGC axon numbers were determined using retrograde fluorescent labelling, and total axons within PN grafts were assessed using pan-neurofilament immunohistochemistry. In the absence of immunosuppression, PN allografts contained few axons and there were very few labelled RGC. These degenerate grafts contained many T cells and macrophages. Systemic (intraperitoneal) application of the immunosuppressants cyclosporin-A or FK506 reduced cellular infiltration into allografts and resulted in extensive axonal regrowth from surviving RGCs. The average number of RGCs regenerating axons into immunosuppressed allografts was not significantly different from that seen in PN autografts in rats sham-injected with saline. Many pan-neurofilament-positive axons, a proportion of which were myelinated, were seen in immunosuppressed allografts, particularly in proximal regions of the grafts toward the optic nerve-PN interface. This study demonstrates that PN allografts can support axonal regrowth in immunosuppressed adult hosts, and points to possible clinical use in CNS repair.
School of Anatomy and Human Biology, The Western Australian Institute for Medical Research, The University of Western Australia, Crawley, Perth, Australia.
Russell S
RS
Gillon
Qi
Q
Cui
Sarah A
SA
Dunlop
Alan R
AR
Harvey
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D020221:Optic Nerve Injuries / Q000601:surgery; D010525:Peripheral Nerves / Q000166:cytology / Q000637:transplantation; D010543:Peroneal Nerve / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation; D016559:Tacrolimus / Q000494:pharmacology*; D014182:Transplantation, Autologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus