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(Investigative Ophthalmology and Visual Science. 2004;45:851-856.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.03-0365
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A Novel Neuroprotectant against Retinal Ganglion Cell Damage in a Glaucoma Model and an Optic Nerve Crush Model in the Rat

Kazumi Maeda,1,2 Akira Sawada,1 Masayuki Matsubara,1 Yoshiyuki Nakai,1 Akira Hara,3 and Tetsuya Yamamoto1

1From the Departments of Ophthalmology and 3Tumor Pathology, Gifu University School of Medicine, Gifu, Japan; and 2Research Laboratories, Toyama Chemical Co., Ltd., Toyama, Japan.

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 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.




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B. C. Hains and S. G. Waxman
Neuroprotection by Sodium Channel Blockade with Phenytoin in an Experimental Model of Glaucoma
Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4164 - 4169.
[Abstract] [Full Text] [PDF]


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