Optic nerve regeneration within artificial Schwann cell graft in the adultrat

We investigate whether an artificial graft made by cultured Schwann cell, e xtracellular matrix (ECM) and trophic factors can provide the environment f or the regeneration of retinal ganglion cell (RGC) axons in adult rats. Six kinds of artificial grafts were used: ECM (control); ECM and Schwann cells ; ECM, Schwann cells and either nerve growth factor, brain-derived neurotro phic factor (BDNF) and neurotrophin-4 (NT-4); ECM, Schwann cells, BDNF and NT-4, combined with intravitreal injection of BDNF. The grafts were transpl anted onto the transected optic nerve. RGC regeneration was evaluated by di l retrograde labeling, immunohistochemistry, and electron microscopy at 3 w eeks post-operation. The degree of dil labeled RGC was approximately 2% for ECM alone, and 10% for ECM and Schwann cells (p < 0.01). The labeling incr eased to approximately 20% by administration of neurotrophins. The addition of intravitreous BDNF injection resulted in highest labeling percentage of 30%. Immunohistochemical study showed that axons were association with GAP -43 and cell adhesion molecules. Neurotrophin receptors (Trk-A and Trk-B) w ere detected in nerve fibers both in the retina and in the graft. Remyelina tion was seen by electron microscopic observation. These results demonstrat e that the regeneration of RGC axons is induced with the use of cultured Sc hwann cells and ECM as promoting factors for regrowth. The degree of regene ration was significantly increased by neurotrophins in the grafts and in th e vitreous. (C) 2001 Elsevier Science Inc.