Abstract
Purpose: :
To elucidate the regenerative potential of injured optic nerve(ON).The purpose was to analyze the cellular and mollecular events that control the degenerative and regenerative processes in lower vertebrate such as goldfish and mammals, following controled injury to the optic nerve.Understanding these events may lead to treatments for diseases and trauma that end in blidness.
Methods: :
The right optic nerve of adult rats was completely transected while the vascular supply of the optic nerve and the meninges were undamaged.Hyaluronic acid (HA)-based hydrogel containing supportive factors or self -assembling peptides(SAP) were implanted in the gap generated by the surgery.Surgery and follow up were performed according to the ARVO Rules for treatment and Care of Animals.Two weeks and one month following the injury the animals underwent MRI evaluation.Non injured optic nerve served as control and injured and not implanted nerves served as negative control. In a parallel set of experiments , the right optic nerve of adult goldfish was crushed or cut ( equal numbers in both groups). Two weeks and one momth after injury, markers asociated with degenerative and regenerative process were studied in the optic nerve and retina.
Results: :
The regenerative process in rats was traced in vivo using Mn+ enhancing signal.The signal in non-injured optic nerve was detected in the reina,optic nerve,optic tract,lateral geniculated body and visual cortex.The signals in axotomized axons was detected only in the vicinity of the retina and not in the optic nerve.These results reflect the degenerative process that destroys the ON axons in response to ON injury.Axotomized ONs that were treated with either HA or SAP exhibited marked regeneration of the ON.Collectively, these results demonstrate the potential of bio-material scaffolds to enhance axonal regeneration.When examined the role of repulsive cues on the generation of non-permissive environment, we found that administration of Semaphorin class 3 to injured goldfish optic nerve markedly disrupted the regenerative process in axotomized optic nerve.
Conclusions: :
The optic nerve of lower vertebrates,such as goldfish, is capable of regeneration and regain of function while higher mammals, such as rat, require special modulations of neuronal environment to enable partial regeneration.
Keywords: optic nerve • regeneration • apoptosis/cell death