BACKGROUND: Methylprednisolone (MP) is often used to treat optic nerve injury. However, its effects in experimental crush injury have not been extensively evaluated. METHODS: Adult Sprague-Dawley rats were subjected to a standardized optic nerve crush injury. Animals were treated either with 30 mg/kg MP intravenous bolus followed by subcutaneous injections every 6 hours for 48 hours, or with a drug vehicle alone. RESULTS: The injury resulted in a partial loss of neuronal nuclei-labeled retinal neurons and a corresponding degeneration of axons distal to the injury. EDI-labeled macrophages accumulated at the site of lesion, phagocyting FJ-labeled axonal debris. Regenerative fibers expressing growth associated protein-43 were seen proximal to the lesion, but did not traverse the glial scar. Analysis of optic nerve function using visual evoked potentials showed typical signals in intact animals, which were abolished after injury in MP-treated and untreated animals. CONCLUSIONS: We did not detect any effects of MP on retinal cell survival, macrophage activity at the site of injury, axonal degeneration/regeneration, or visual function. These experimental results provide a physiologic underpinning for the lack of efficacy demonstrated in a large trial of MP treatment of clinical optic nerve injury.
BACKGROUND:Methylprednisolone (MP) is often used to treat optic nerve injury. However, its effects in experimental crush injury have not been extensively evaluated. METHODS: Adult Sprague-Dawley rats were subjected to a standardized optic nerve crush injury. Animals were treated either with 30 mg/kg MP intravenous bolus followed by subcutaneous injections every 6 hours for 48 hours, or with a drug vehicle alone. RESULTS: The injury resulted in a partial loss of neuronal nuclei-labeled retinal neurons and a corresponding degeneration of axons distal to the injury. EDI-labeled macrophages accumulated at the site of lesion, phagocyting FJ-labeled axonal debris. Regenerative fibers expressing growth associated protein-43 were seen proximal to the lesion, but did not traverse the glial scar. Analysis of optic nerve function using visual evoked potentials showed typical signals in intact animals, which were abolished after injury in MP-treated and untreated animals. CONCLUSIONS: We did not detect any effects of MP on retinal cell survival, macrophage activity at the site of injury, axonal degeneration/regeneration, or visual function. These experimental results provide a physiologic underpinning for the lack of efficacy demonstrated in a large trial of MP treatment of clinical optic nerve injury.