A segment of optic nerve transplanted intravitreally retards death and enhances axonal regneration of retinal ganglion cells in adult hamsters

Abstract

We have shown that co-transplantation of intravitreal peripheral nerve (PN) and optic nerve (ON) graft rather than the PN graft alone, induces more retinal ganglion cells (RGCs) to sprout axon-like processes (ALPs). In the present study, the effect of intravitreal PN and ON graft on the survival and regeneration of hamster RGCs was investigated. A nerve graft (PN, ON and nonviable nerve) was transplanted into the vitreous following an intraorbital transection of ON. Two days before sacrificing the hamsters, FluoroGold (FG) was administered to the transected site of ON and the number of FG-labeled RGCs (mean 6 S.D.) was estimated in wholemounted retinas at 5, 7 and 14 days post-axotomy (dpa). Comparing with the number of RGCs following axotomy, there were significantly more RGCs after transplanting the ON graft at 5 (54495 6 3783.3 P , 0.05) and 7 (38510 6 3151.1 P , 0.001) dpa. The PN graft exerted no survival effect on RGCs at all time points (P . 0.05). To study the effect of intravitreal nerve graft on RGCs regeneration, a long PN graft was attached to the proximal stump of ON (,1.5 mm from optic disc) followed by an intravitreal nerve (PN, ON, PN 1 ON or non-viable nerve) transplantation. After 4 weeks of operation, FG was applied to the transected long PN graft. Retinas receiving the intravitreal PN graft (1230 6 438.83, P , 0.05) or the ON graft (1280 6 496, P , 0.05) contained significantly more regenerating RGCs than retinas without the nerve graft (608 6 124.84). The PN 1 ON grafts (1913 6 705.36, P , 0.01) induce significantly more regenerating RGCs than that of the PN or ON graft. Although both PN and ON grafts enhance regeneration of RGCs, ON graft retards death of RGCs whereas PN graft cannot. Thus, different mechanisms may be operated by PN and ON grafts regarding axonal regeneration.