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S.S. Samudre, P.B. Williams, B.R. Martin, I.G. Castillo, A. Hosseini, F.A. Lattanzio, Jr.; Novel Endocannabinoids Confer Neuroprotection in NMDA Rat Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1566.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucomatous damage to the retina and optic nerve progresses even after therapy to maintain normal intraocular pressure (IOP). Topical application of endogenous cannabinoid analogs decreases IOP in a rat model of glaucoma. Based upon their effects on other tissues, we hypothesize that these analogs may also confer direct neuroprotective effects on the retina, possibly via CB1 and/or CB2 receptors. The purpose of this study is to determine if these novel CB agonists, lipid soluble O–1812 (CB1> 2), and water soluble O–2545 (CB 1, 2) confer retinal neuroprotection.
Retinal damage was induced by intravitreal injection of NMDA (2 µl of 10 mM) in Sprague–Dawley rats. In other groups 2 µl O–1812 (2 mM) or 2 µl O–2545 (2mM) were co–injected with NMDA. Electroretinograms (ERG) were recorded at baseline, 1 wk and 2 wk after injection. Contralateral normal eyes served as controls. After 2 wk, retinas were flat mounted and stained with H&E. In other experiments, IOP was obtained following topically applied O–1812 or O–2545.
At 1 wk, a–wave amplitude in all treatments was depressed with no functional change in b–wave. O–1812 was most effective in restricting functional loss of a–wave amplitude. At 2 wk, a–wave amplitudes improved only in drug treated group. O–1812 most effectively restored a–wave amplitude towards baseline; O–2545 was less effective. The a–wave amplitude in NMDA treated group continued to decline with the damage extending to b–wave amplitude. Both drugs significantly reduced IOP by 79 % 30 min after O–1812; by 78 % 60 min after O–2545 (p<0.05). Retinal whole mounts after NMDA alone showed areas devoid of cells, while those treated with O–1812 and O–2545 were intact with an even distribution of retinal ganglionic cells.
Both compounds partially preserved functional a–waves, completely prevented b–wave loss, and maintained a normal distribution of ganglionic cells. Considering both IOP and neuroprotective effects, lipid soluble O–1812 was most effective.
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