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A.S. Solomon, A. Nitzan, P. Kermer, A. Shirvan, M. Bahr, A. Barzilai; Cellular and Molecular MechanismUnderlying Optic Nerve Degeneration and the Creation of a Non–Permissive Environment for Regeneration Following Axotomy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):727.
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To determine the mechanisms underlying the generation of a non–permissive environment preventing axonal growth by analyzing the molecular and cellular alterations that occur in response to acute optic nerve injury.
A rat model of complete transection of the optic nerve that spares the vascular supply and the neural scaffold was used. The response of the optic nerve and retinas to axotomy was studied by immunological and biochemical investigations.
Optic nerve axotomy led to massive cell invasion at the site of injury that spread along both sides of the nerve. The invading cells were microglia, oligodendrocytes, and to a lesser extent astrocytes. Myelin debris was not completely removed from the site of injury or from along the optic nerve. A marked induction of type 3 semaphorin was evident in response to axotomy, especially in the area of the scar, and persisted for the 28 days of the experiment. The molecular events associated with axotomy were studied by measuring the levels of the pro–apoptotic protein Bax, p38 and ERK1/2. The levels of Bax were elevated 3 days post–axotomy and then declined. Optic nerve axotomy led to the activation of p38 and ERK1/2. In addition, acute nerve injury led to morphological alterations in oligodendrocytes, astrocytes and the extracellular matrix, disrupting the delicate internal organization of the optic nerve.
We suggest that cell invasion, semaphorin induction, the presence of myelin debris, and disruption of the internal organization of the optic nerve contribute to the generation of the non–permissive environment that prevents axonal regeneration and leads to neuronal loss.
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