A novel neuroprotectant against retinal ganglion cell damage in a glaucoma model and an optic nerve crush model in the rat.
OBJECTIVE
To investigate the effects of repeated treatments with a neuroprotective compound, R(-)-1-(benzo [b] thiophen-5-yl)-2-[2-(N, N-diethylamino) ethoxy] ethanol hydrochloride (T-588), on retinal ganglion cell (RGC) survival in rat eyes with elevated intraocular pressure (IOP) or after optic nerve crush.


METHODS
An increase in IOP was induced by a single laser treatment to the trabecular meshwork in one eye of adult Wistar rats. Crush injury was unilaterally produced by clipping the optic nerve 2 mm behind the globe. RGC density was estimated by counting fluorescent dye-labeled cells in the flatmount of the retina. The optic nerve damage in the crush model was also evaluated histologically.


RESULTS
In the elevated IOP model, RGC survival decreased to 72.9% +/- 3.8% (mean +/- SEM) of that of the contralateral control eye on the eighth day after laser irradiation. Repeated treatments with T-588 at 30 mg/kg twice daily significantly enhanced RGC survival (86.0% +/- 2.2%, P = 0.0242) without the reduction of IOP. In the optic nerve crush model, RGC survival diminished to 37.2% +/- 8.4% of that of the contralateral control eye after 4 weeks. Repeated applications with T-588 at 10 mg/kg twice daily significantly enhanced RGC survival (77.8% +/- 2.1%, P = 0.0038). Histologically, the rat optic nerve in the group treated with T-588 at 10 mg/kg retained a near-normal morphology.


CONCLUSIONS
T-588 has a neuroprotective effect against RGC death caused by elevated IOP and optic nerve crush in the rat.
Maeda
Kazumi
K
Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
Sawada
Akira
A
Matsubara
Masayuki
M
Nakai
Yoshiyuki
Y
Hara
Akira
A
Yamamoto
Tetsuya
T
D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004048:Diethylamines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007429:Intraocular Pressure; D008297:Male; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000150:complications; D009900:Optic Nerve / Q000601:surgery; D009901:Optic Nerve Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D013876:Thiophenes / Q000627:therapeutic use*
D004048:Diethylamines; D018696:Neuroprotective Agents; D013876:Thiophenes; C082372:T 588