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Ronald Lai, Raymond Lim, George Wu, Jeffrey L. Edelman; A Comparative Study Of The Effect Of Brimonidine, Fenretinide and Valproate On Light-induced Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5466. doi: https://doi.org/.
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It has been suggested that brimonidine, fenretinide and valproate may have beneficial effects for the treatment of retinal degeneration. Since these agents have different pharmacological properties, it is believed that they mediate retinal protection via different mechanisms. In this study, we examined and compared the effect of these compounds in the blue light-induced retinal degeneration rat model.
Male Spraque-Dawley rats were dosed daily for 10 days with either brimonidine (1 mg/kg ip), fenretinide (5 mg/kg oral), or sodium valproate (250 mg/kg ip). Vehicle-treated animals served as controls. On the third dosing day, the animals were dark adapted for 24 hours and then exposed to 8 hours of blue light (4000 lux). The change in retinal function of these animals was evaluated using electroretinography (ERG) after 7 days of recovery period. Histologic assessment of the light-induced retinal damage was performed on the sections of paraffin-embedded eyes. Evaluation of the cone photoreceptor damage was performed on PNA-stained retinal flatmounts.
Seven days after blue light exposure, the photoreceptor layer in the superior side of the retina was reduced from 12 rows of cells to 1 row, and ERG a-wave was decreased by 80%. Number of healthy cone photoreceptor was significantly reduced in the superior retina. Increased autofluorescence deposits were also observed at the RPE/photoreceptor layers. At 1 mg/kg dose, brimonidine protected the photoreceptor layer by 45% and the ERG a-wave by 50%. At 5 mg/kg dose, fenretinide provided 26% protection in the outer nuclear layer and 30% protection in ERG a-wave amplitude, compared with controls. However, no observable difference was found between vehicle-treated animals and valproate-treated animals.
Both brimonidine and fenretinide (but not valproate) significantly ameliorate photoreceptor damage in this blue light-induced retinal degeneration model. Brimonidine appears to be more efficacious than fenretindie in protecting the photoreceptor, which may be due to the different protective mechanisms mediated by these two agents.
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