PURPOSE: Analyzing cellular behavior during scar formation and determining the expression of growth inhibiting molecules in the optic nerve and retina following acute optic nerve injury. METHODS: 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 approaches. RESULTS: Optic nerve axotomy led to massive cell invasion at the site of injury that spread along both sides of the nerve. The cells were microglia, oligodendrocytes, and to a lesser extent astrocytes. A marked induction of semaphorin 3A was evident, especially in the area of the scar, and persisted up to the 28th day of the experiment. Expression of neuropilin-1, a component of the semaphorin 3A receptor, increased following injury. The molecular events associated with axotomy were studied by measuring the levels of semaphorin 3A, p38 MAPK, and ERK1/2 in the retina. Semaphorin 3A levels and the activated form of p38 were elevated 3 days post-axotomy and then declined; ERK1/2 activation levels reached their peak 14 days post axotomy. Acute nerve injury led to morphological alterations in oligodendrocytes, astrocytes, and the extracellular matrix, disrupting the delicate internal organization of the optic nerve. CONCLUSIONS: We suggest that cell invasion, semaphorin 3A and neuropilin-1 induction, and disruption of the internal organization of the optic nerve contribute to axotomy-induced degenerative processes.
PURPOSE: Analyzing cellular behavior during scar formation and determining the expression of growth inhibiting molecules in the optic nerve and retina following acute optic nerve injury. METHODS: 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 approaches. RESULTS: Optic nerve axotomy led to massive cell invasion at the site of injury that spread along both sides of the nerve. The cells were microglia, oligodendrocytes, and to a lesser extent astrocytes. A marked induction of semaphorin 3A was evident, especially in the area of the scar, and persisted up to the 28th day of the experiment. Expression of neuropilin-1, a component of the semaphorin 3A receptor, increased following injury. The molecular events associated with axotomy were studied by measuring the levels of semaphorin 3A, p38MAPK, and ERK1/2 in the retina. Semaphorin 3A levels and the activated form of p38 were elevated 3 days post-axotomy and then declined; ERK1/2 activation levels reached their peak 14 days post axotomy. Acute nerve injury led to morphological alterations in oligodendrocytes, astrocytes, and the extracellular matrix, disrupting the delicate internal organization of the optic nerve. CONCLUSIONS: We suggest that cell invasion, semaphorin 3A and neuropilin-1 induction, and disruption of the internal organization of the optic nerve contribute to axotomy-induced degenerative processes.