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A. Oyejide, J. Burke, B. Short, L. Wheeler; Oral Memantine Preserves Retinal Histology in Rabbits Exposed to Acute Ischemic Damage . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5053.
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To evaluate the effects of a single oral dose of memantine (20 mg/kg) on retinal histology produced by an acute retinal ischemic insult in rabbits
Dutch–belted rabbits weighing approximately 2.5 kg received either a single oral dose of 20 mg/kg memantine or 50 mg sugar in a gelatin capsule. Two hours later, rabbits were anesthetized with isofluorane, and unilateral acute retinal ischemia was induced by raising intraocular pressure to 120 mm Hg for 45 minutes following gravity flow injection of PBS into the anterior chamber. A drop of topical proparacaine anesthetic was placed on the cornea prior to needle insertion. At 6 months, animals were humanely sacrificed, enucleated and eyes fixed in Davidson’s fixative. Paraffin–embedded sections (5 um) were processed to H&E staining. Additional sections were also immunostained for the expression of GFAP antigen.
Pressure induced global ischemia caused marked retinal injury in vehicle–treated eyes The ischemic lesion was characterized by disorganization, degeneration and necrosis of cells in all retinal layers, resulting in moderate to severe attenuation of the retina. The photoreceptor layer was most severely and consistently affected. The RPE layer showed multifocal hypertrophy and hyperplasia, occasionally associated with microthrombi in the subjacent choriocapillaris. In focal areas of marked retinal necrosis, subretinal fibrovascular plaques were evident. There was a marked increase in the immunoreactivity of GFAP antigen in retinal sections from the placebo–treated ischemic eye when compared to the fellow untreated eye. In memantine –treated eyes subjected to pressure –induced ischemia cell degeneration and necrosis was significantly reduced in all retinal levels in comparison to vehicle–treated ischemic (OD) eyes. In addition, increased GFAP immunoreactivity of pressure –induced ischemic retina was significantly attenuated by memantine.
These data suggest that oral memantine may protect the retina against the degenerative and necrotic lesions classically associated with acute ischemic insult.
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