Primary amines protect against retinal degeneration in mouse models of retinopathies.
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| 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.
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| Authors | Akiko Maeda, Marcin Golczak, Yu Chen, Kiichiro Okano, Hideo Kohno, Satomi Shiose, Kaede Ishikawa, William Harte, Grazyna Palczewska, Tadao Maeda, Krzysztof Palczewski |
| Journal | Nature chemical biology (Nat Chem Biol) Vol. 8 Issue 2 Pg. 170-8 (Dec 25 2011) ISSN: 1552-4469 [Electronic] United States |
| PMID | 22198730 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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