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(Investigative Ophthalmology and Visual Science. 2000;41:2967-2971.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

The Combined Effect of Brain-Derived Neurotrophic Factor and a Free Radical Scavenger in Experimental Glaucoma

Mei–Lan Ko1,2,4, Dan–Ning Hu3,4,6, Robert Ritch4,6 and Sansar C. Sharma5,6

1 From the Department of Physiology, National Taiwan University, Taipei; the 2 Department of Ophthalmology, Hsin–Chu Hospital, Taiwan; the 3 Departments of Pathology and Laboratory Medicine and 4 Ophthalmology, New York Eye and Ear Infirmary, New York, New York; and the 5 Departments of Cell Biology and 6 Ophthalmology, New York Medical College, Valhalla, New York.

PURPOSE. Brain-derived neurotrophic factor (BDNF) had a limited effect on the survival of retinal ganglion cells (RGCs) in rats’ eyes with elevated intraocular pressure (IOP). The combined treatment of BDNF and a nonspecific free radical scavenger N-tert-butyl-(2-sulfophenyal)-nitrone (S-PBN) was investigated on the RGCs in hypertensive eyes of rats.

METHODS. Adult Wistar rats were separated into five groups: BDNF (0.5 µg) + S-PBN; BDNF (1.0 µg) + S-PBN; BDNF (1.0 µg); S-PBN; and phosphate-buffered saline. Right eyes served as normal controls (n = 10). RGCs were labeled with 5% Fluoro Gold; injected into the superior colliculus. Three days after intratectal injection, the episcleral veins of the left eyes were cauterized. Intravitreal injection of BDNF was performed on days 5, 13, 21, and 29 after IOP elevation. S-PBN was injected intraperitoneally (100 mg/kg body wt) every 12 hours starting 30 minutes after cauterization.

RESULTS. The survival of RGCs using BDNF treatment alone in moderately hypertensive eyes and systemic administration of S-PBN alone did not significantly rescue the RGCs. However, the combination of BDNF and S-PBN increased the survival of RGCs to 90.1%.

CONCLUSIONS. Trophic factors and antioxidants have synergistic effects on rescuing RGCs from death in eyes with elevated IOP. Further studies of different combined treatment therapies may provide avenues to save RGCs from death in eyes with elevated IOP.




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