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Beata Jastrzebska, Songqi Gao, Grazyna Palczewska, Marcin Golczak, Zhigian Dong, Krzysztof Palczewski; Protective effect of unbleachable retinal chromophore analogue against light-induced retinal degeneration in mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):369.
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Excessive light can be detrimental to retinal heath. Prolonged exposure to bright light leads to buildup of retinal by-products in the photoreceptor cells when their clearance is compromised. Affected chromophore regeneration also results in accumulation of free constitutively active opsin, which accelerates retinal degeneration. We aimed to test if silencing opsin activity by treatment with unbleachable retinal chromophore analogue would prevent retinal damage in mice susceptible to light-induced retinopathy.
The Abca4-/-Rdh8-/- mice that lack both the ATP-binding cassette transporter 4 (ABCA4) and all-trans-retinol dehydrogenase (RDH8) enzyme exhibit severe retinal degeneration after acute light stimulation. The effects of unbleachable retinal chromophore analogue in mice IP-injected with this retinal 30 min prior to exposure of 10,000 lux light for 30 min were tested 7-14 days later. Multiple in vivo imaging techniques OCT, SLO, TPO and an in vitro histological analysis were used to assess retinal morphology. Changes in the visual function were tested by electroretinogram (ERG) measurements. Quantitative LC-MS analysis was used to determine the accumulation of used retinal analogue in the mice eyes.
The Abca4-/-Rdh8-/- mice exhibited pronounced light-induced morphological changes in rod and cone photoreceptors. This morphological damage was largely diminished in mice treated with unbleachable retinal chromophore analogue. Thinning of the outer nuclear layer (ONL) and accumulation of autofluorescent spots were almost completely prevented in treated mice as compared to control mice. Retinal function was also preserved in retinal analogue-treated mice. As determined by ERG, both scotopic and photopic b-waves of these mice were very similar to those of mice kept in the dark. Quantitative LC-MS analysis revealed additive accumulation of this retinoid in the eyes after multiple administrations, strongly indicating its stable binding to opsin protein
All together, this study provides evidence that eliminating an accumulation of unliganded opsin is critical to prevent bright light-induced retinal degeneration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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