The combined effect of brain-derived neurotrophic factor and a free radical scavenger in experimental glaucoma.
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 microg) + S-PBN; BDNF (1. 0 microg) + S-PBN; BDNF (1.0 microg); 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.
Ko
M L
ML
Department of Physiology, National Taiwan University, Taipei.
Hu
D N
DN
Ritch
R
R
Sharma
S C
SC
D000818:Animals; D001557:Benzenesulfonates / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D002452:Cell Count; D002470:Cell Survival; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007429:Intraocular Pressure; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D014822:Vitreous Body
D001557:Benzenesulfonates; D019208:Brain-Derived Neurotrophic Factor; D016166:Free Radical Scavengers; C094272:N-tert-butyl-(2-sulfophenyl)nitrone