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Nat Chem Biol. 2011 Dec 25;8(2):170-8. doi: 10.1038/nchembio.759.

Primary amines protect against retinal degeneration in mouse models of retinopathies.

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  • 1Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, USA.

Abstract

Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore 11-cis-retinal and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the photoisomerized product, all-trans-retinal, can cause severe retinal pathology. Here we lowered peak concentrations of free all-trans-retinal with primary amine-containing Food and Drug Administration (FDA)-approved drugs that did not inhibit chromophore regeneration in mouse models of retinal degeneration. Schiff base adducts between all-trans-retinal and these amines were identified by MS. Adducts were observed in mouse eyes only when an experimental drug protected the retina from degeneration in both short-term and long-term treatment experiments. This study demonstrates a molecular basis of all-trans-retinal-induced retinal pathology and identifies an assemblage of FDA-approved compounds with protective effects against this pathology in a mouse model that shows features of Stargardt's disease and age-related retinal degeneration.

PMID:
22198730
[PubMed - indexed for MEDLINE]
PMCID:
PMC3518042
Free PMC Article
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