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R.K. Lai, T. Chun, L.A. Wheeler, S.M. Whitcup; Tazarotene, a Retinoic Acid Receptor (RAR) Agonist, Protects Photoreceptor in a Blue Light–Induced Retinal Degeneration Model . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1659.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: 13–cis retinoic acid has recently been shown to protect photoreceptor from light–induced damage. In vivo, 13–cis retinoic acid can be metabolized to metabolites that may interact with either the RAR or RXR retinoid receptor subtypes. In this study, we investigated whether RAR receptor subtype specific compounds would exhibit photoreceptor protection. We examined the effect of Tazarotene, a specific RAR retinoid receptor subtype agonist, in a blue light–induced retinal degeneration rat model. Methods: Male Spraque–Dawley rats were orally dosed with 0.1, 0.3, 1 or 3 mg/kg Tazarotene for five days. Another set of animals were orally treated with 3 mg/kg Tazarotene plus 3 mg/kg AGN194310, a specific RAR receptor subtype antagonist for five days. Animals dosed with vehicle served as controls. On the fourth dosing day, the animals were dark adapted for 24hr. They were then exposed to 8 hours of high intensity blue light (12000 Lux) following the fifth dose. The retinal function of the animals was evaluated using electroretinography (ERG) after 5 days of resting in a dark environment. Histologic signs of light damage were assessed on sections of paraffin embedded eyes. Results: After blue light exposure, the photoreceptor layer in the superior side of the retina was reduced from 12 rows of cells to 1 row. The ERG a–wave was significantly decreased by 73%. Tazarotene treatment dose–dependently protected the photoreceptor layer and the ERG a–wave. At 3 mg/kg dose, Tazarotene provided 36% protection in the outer nuclear layer thickness and 17% protection in ERG a–wave amplitude, compared with controls. These protective effects were blocked by co–treatment of specific RAR receptor subtype antagonist, AGN194310. Conclusions: Tazarotene dose–dependently ameliorates photoreceptor damage in a blue light–induced retinal degeneration model. The protection is mediated through the RAR retinoid receptor since it can be blocked by a RAR retinoid receptor antagonist.
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