Cable grafting of peripheral nervous system in optic nerve damage

Damage to retinal ganglion cell axons from injury or disease can lead to rapid and sustained axonal loss resulting in permanent loss of neural function and blindness. If this damage is sustained early in life, target areas in the central nervous system (CNS) may have altered architecture and function. Currently there is no effective treatment to reverse permanent loss of function. Therefore, there is a need to establish a therapeutic approach to bypass optic nerve axonal loss and rescue ganglion cells. To date studies to bypass transected optic nerve using peripheral nervous system (PNS) grafts from optic nerve head to superior colliculus have been promising. However, there is limited knowledge regarding long term survivability, overall effectiveness and functional integrity of PNS grafts thereby limiting their routine therapeutic use. Purpose: The aim of this study was to establish an adult model optic nerve cable graft technique, and to examine if this technique can preserve CNS architecture in a neonatal model after unilateral optic nerve transection. Methody Using adult female Wistar rats (200 g), a section of autologous sciatic nerve was dissected and attached to a unilaterally transected optic nerve close to the optic nerve head. The distal end was attached to the ipsilateral superior colliculus region of the brain at the time of initial surgery or in a delayed fashion 8 weeks later. The same technique was used in 15 day old Wistar neonatal rats with connection to the ipsilateral superior colliculus at the time of initial surgery. To identify axonal connections between optic nerve and superior colliculus target, sections of retina, optic nerve graft and superior colliculus were examined at 20 weeks following intravitrial injection of Horse Radish Peroxidase (HRP) for HRP immunohistochemistry. Architecture of the superior colliculus was also assessed. Conclusions: This research has potential clinical applications in the understanding of ophthalmological conditions such as optic nerve crush, optic nerve tumors and glaucoma.