Neuroprotective effect of nipradilol [3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran] in a rat model of optic nerve degeneration.
OBJECTIVE
Currently, nipradilol, an alpha-1 beta-blocker with a nitric oxide donative action, is used as an ocular hypotensive agent for glaucoma patients in Japan. The aim of the present study was to investigate the neuroprotective effect of nipradilol on optic nerve injury in rats.


METHODS
Using a calibrated cross-action forceps, a crush lesion was inflicted unilaterally on the optic nerve 2 mm behind the globe of adult Wistar albino rats and followed by topical instillation of either 0.25% nipradilol or the vehicle in both eyes twice daily until killing. A sham operation was conducted on the contralateral eye. Intraocular pressure measurement was performed 3 days before and 4, 7, 14, 21, and 28 days after acute injury of the optic nerve. One week before killing, Fluoro-Gold was injected into the bilateral superior colliculi to identify surviving retinal ganglion cells (RGCs).


RESULTS
Twenty-eight days after injury, retinal damage was assessed morphologically. There was no significant difference in the intraocular pressure of both eyes between the nipradilol and control groups. Within 1 month, the mean RGC density in the vehicle-treated group had decreased to 71.58+/-0.102% of that of the contralateral eye, whereas the optic nerve crush with topical application of nipradilol showed a considerably smaller decrease to 89.60+/-0.027% (P<0.001). No significant morphologic difference between sham-operated animals and animals from the experimental groups was observed in the retinal layers owing to the crush force.


CONCLUSIONS
Our findings might indicate that nipradilol can alleviate RGC death induced by optic nerve crush injury in the rat.
Karim
Md Zahidul
MZ
Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan. mdzkarim2003@yahoo.com
Sawada
Akira
A
Mizuno
Ken
K
Kawakami
Hideaki
H
Ishida
Kyoko
K
Yamamoto
Tetsuya
T
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D007429:Intraocular Pressure; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020221:Optic Nerve Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011412:Propanolamines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D011412:Propanolamines; C036089:nipradilol