| First Author | Maeda A | Year | 2011 |
| Journal | Nat Chem Biol | Volume | 8 |
| Issue | 2 | Pages | 170-8 |
| PubMed ID | 22198730 | Mgi Jnum | J:280311 |
| Mgi Id | MGI:6368450 | Doi | 10.1038/nchembio.759 |
| Citation | Maeda A, et al. (2011) Primary amines protect against retinal degeneration in mouse models of retinopathies. Nat Chem Biol 8(2):170-8 |
| abstractText | 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. |
