Combinations of self-assembling peptide nanofiber scaffold and chondroitinase-ABC appear to create a more permissive environment in optic tract brain lesion repair resulting in return of vision

Abstract

Purpose:: Neurons in the adult mammalian central nervous system (CNS) have limited capability to regenerate their axons after injury. It is generally accepted that the inability of CNS axons to regenerate is partly due to the local environment of the injured CNS axons. Traumatic injury in the CNS is often followed by a robust glial reaction and the failure of CNS axons to regenerate is partly attributed to the inhibitory surface of the glial scar and extracellular matrix (ECM) produced by oligodendrocytes and astrocytes. Furthermore, a tissue gap formed after traumatic injury would completely block the reinnervation of the CNS axons.

Methods:: In this experiment, the brachium of the superior colliculus was completely transected in a group of 38 adult golden hamsters and 20 µl of 1% self-assembling peptide nanofiber scaffold (SAPNS) and/or 2.5 units/ml (final concentration) Chondroitinase-ABC were injected into the lesion site. The progression of axonal regeneration and the reinnervation of the superior colliculus were monitored at 4, 6, and 12 weeks following the lesion by intravitreal injection of CTB-FITC. Each animal was tested every other day for 12 weeks by presenting stimulus that consisted of a seed and small cork.

Results:: We found that SAPNS and Chondroitinase-ABC used together, facilitated retinal ganglion cell (RGC) axons to regenerate across the lesion site. The combination of SAPNS and Chondroitinase-ABC had a synergistic effect evidenced by the larger area of reinnervation than either the SAPNS or Chondroitinase-ABC. This effect was observed in all treatment groups as early as four weeks after the transection, while saline controls showed no reinnervation at any time point. The adult hamsters showed a functional return of vision in the SAPNS/Chondroitinase-ABC treated cases beginning at 6 weeks post-surgery.

Conclusions:: The SAPNS/Chondroitinase-ABC combination offers an effective new means of creating a more permissive environment for growth after traumatic injury to the CNS, allowing regrowth of axons into the denervated site evidenced by functional return of vision.