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BACKGROUND: Previous studies have shown that nerve regeneration factor (NRF) provides neuroprotective effects. However, the neuroprotective effects on retinal ganglion cells in an animal model of glaucoma remain uncertain. OBJECTIVE: To determine the neuroprotective effects of NRF on retinal ganglion cells in a rabbit model of acute hyper-intraocular pressure and to compare the effects on brain-derived neurotrophic factor (BDNF).DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at Jiangsu Provincial Key Laboratory of Neural Regeneration from September 2006 to August 2007.MATERIALS: Sterone, a major component of NRF, was provided by the Key Laboratory of Neural Regeneration, Nantong University in China; BDNF was provided by BioDesign Inc., USA.METHODS: A total of 24 healthy rabbits were randomly assigned to NRF, BDNF, and phosphate buffered saline groups, with 8 rabbits per group. The left eyes were considered normal controls, and acute hyper-intraocular pressure was induced in the right eyes via anterior chamber perfusion. The right camera vitrea bulbi was injected with 4.5 μg NRF, 3.75 μg BDNF, or 5 μL 0.1 mol/L phosphate buffered saline, respectively. MAIN OUTCOME MEASURES: Retinal ganglion cells were reverse-labeled using horseradish peroxidase to quantify cell density at 2, 4, and 6 mm from the optic disc edge. RESULTS: NRF increased the number of surviving retinal ganglion cells at the optic disc edge (P < 0.01 or P < 0.05). The density of surviving retinal ganglion cells decreased with increasing distance from the optic disc. The number of retinal ganglion cells in the BDNF group was similar to the NRF group (P > 0.05). At 2, 4, and 6 mm away from the optic disc edge, there was no significant difference in retinal ganglion cell density between NRF and BDNF groups (P > 0.05). CONCLUSION: NRF provided protection to retinal ganglion cells in a rabbit model of acute hyper-intraocular pressure, i.e., NRF enhanced the survival rate of retinal ganglion cells. The neuroprotective effect was similar to BDNF.