Time-Dependent Effects of Reduced Cerebrospinal Fluid Pressure on Optic Nerve Retrograde Axonal Transport

PURPOSE: To study the time-dependent effects of reduced cerebrospinal fluid pressure (CSFP) on axonal transport in the rat optic nerve. METHODS: Seventy-two adult Sprague Dawley rats were used for this study. Fluoro-Gold was injected into the superior colliculi to study axonal transport. CSFP was reduced to 1.5 to 2.9 mm Hg by continuous aspiration of cerebrospinal fluid. In the sham control group (n = 18), a trocar was implanted in the cisterna magna, but cerebrospinal fluid was not released. CSFP and intraocular pressure (IOP) were continually monitored. CSFP was reduced for 1 hour (low-CSFP-1h study group; n = 18), 3 hours (low-CSFP-3h study group; n = 18), or 6 hours (low-CSFP-6h study group; n = 18) before the animals were euthanized. Confocal microscopy was used to compare axonal transport in different quadrants of the retina between control and low-CSFP eyes. RESULTS: Changes in axonal transport were observed only after 3 hours of CSFP reduction and not in the low-CSFP-1h study group. These changes occurred in a time-dependent manner, with 6 hours of CSFP reduction producing the longest lasting and most severe reduction in fluorescence. CONCLUSIONS: The time-dependent changes observed in axonal transport in the optic nerve provide further evidence regarding the pathogenesis of axonal damage caused by reduced CSFP.