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Abstract #10164 Published in IGR 6-1

A novel neuroprotectant against retinal ganglion cell damage in a glaucoma model and an optic nerve crush model in the rat

Maeda K; Sawada A; Matsubara M; Nakai Y; Hara A; Yamamoto T
Investigative Ophthalmology and Visual Science 2004; 45: 851-856


PURPOSE: 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 four 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.

Dr. K. Maeda, Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan


Classification:

11.8 Neuroprotection (Part of: 11 Medical treatment)



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