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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Maeda A,Golczak M,Chen Y,Okano K,Kohno H,Shiose S,Ishikawa K,Harte W,Palczewska G,Maeda T,Palczewski Kdoi
10.1038/nchembio.759subject
Has Abstractpub_date
2011-12-25 00:00:00pages
170-8issue
2eissn
1552-4450issn
1552-4469pii
nchembio.759journal_volume
8pub_type
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