Neuroprotective effect of nipradilol on axotomized rat retinal ganglion cells.
OBJECTIVE
To determine whether nipradilol, a new anti-glaucoma drug, can protect retinal ganglion cells (RGCs) from secondary cell death caused by transection of the optic nerve (ON).


METHODS
The ON was transected 0.7 mm from its exit from the eye in Sprague Dawley rats. Nipradilol (1 x 10(-8) - 10(-3) M), timolol, prazosin, or sodium nitroprusside (SNP) (1 x 10(-6) - 10(-4) M) was injected intravitreally fifteen-minutes before the ON transection. Control eyes received the same amount of phosphate buffered (PB). The RGCs were labeled retrogradely by placing gelfoam soaked in fluoro-gold (FG) on the stump of ON. RGCs density was determined by counting the FG-labeled RGCs in flat-mounted retinas 3 to 14 days post-transection. To determine whether the neuroprotective action of nipradilol was due to its NO-donor property, carboxy-PTIO, a NO-scavenger, or KT5832, a protein kinase G inhibitor, was injected with the nipradilol.


RESULTS
After ON transection, the number of surviving RGCs after intravitreal injection of 1 x 10(-4) M nipradilol was significantly higher than that following PB injection. This protective activity was dose-dependent. Neither timolol nor prazosin had a neuroprotective effect but SNP protected RGCs in a dose-dependent manner. Carboxy-PTIO and KT5832 decreased the neuroprotective effect of nipradilol.


CONCLUSIONS
These results indicate that nipradilol has a possibility of neuroprotective effect on axotomized RGCs, and the effect depended mainly on its NO-donor property.
Department of Ophthalmology, Tohoku University School of Medicine, Sendai, Japan. ntoru@fa2.so-net.ne.jp
Toru
T
Nakazawa
Hiroshi
H
Tomita
Katsuhiro
K
Yamaguchi
Yumi
Y
Sato
Masahiko
M
Shimura
Soichiro
S
Kuwahara
Makoto
M
Tamai
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D019771:Axotomy; D016923:Cell Death; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology
D018674:Adrenergic Antagonists; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D011412:Propanolamines; D009599:Nitroprusside; D009569:Nitric Oxide; C036089:nipradilol