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A. S. Solomon, S. Rosenzweig, A. Nitzan, A. Barzilai; Analysis of Cellular and Molecular Events Associtated With Optic Nerve Degeneration and Regeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4353. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate the regenerative potential of injured optic nerve(ON).Results are presented of a study on the regenerative potential of CNS mammalian axons using our unique rat optic nerve model of complte axotomy. The purpose was to analyze the cellular and molecular events that control the degenerative and regenerative process in lower vertebrate such as goldfish, and mammals, following trauma to ON . Understanding the events may lead to treatments for diseases and trauma that end in blindness.
The right ON of adult rats was completely transected while the vascular supply and the neural scafold were left intact.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 after the surgical procedure the animals underwent MRI evaluation of the visual pathway.Non-injured ON served as positive control and complete transected nerve served as negative control.In a parallel set of experiments, under deep anesthezia, the right optic nerve of adult goldfish was crushed or cut ( equal number of fish in each group) . Two weeks and one month after injury , markers asocited with degenerative and regenerative processes were studied in the optic nerve and retina. Semaphorin class 3 was administred to goldfish optic nerve to examine whether the degenerative process could be interrupted.
The regenerative process was traced in vivo using Mn+ enhancing signal. The signal in non-injured optic nerve was detected from the retina to the visual cortex.The signal in complete transected optic nerves was detected only in the retina.Axotomized ONs treated with HA or SAP demonstrated signals along the ON. In vitro confocal imaging of the optic nerves confirmed the MRI axonal regeneration image. Collectively, these results demonstrate the potential of bio-material scaffolds to enhance axonal regeneration. When we examined the role of repulsive cues on the generation of non-permisive environment, we found that administration of Semaphorin class 3 to injured optic nerve of goldfish optic nerve markedly disrupted the regenerative process in axotomized nerve.
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