Primary amines protect against retinal degeneration in mouse models of retinopathies

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / pharmacology
  • Amines / therapeutic use*
  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Macular Degeneration / drug therapy
  • Mice
  • Retinal Degeneration / drug therapy
  • Retinal Degeneration / prevention & control*
  • Retinaldehyde / therapeutic use
  • Schiff Bases / analysis
  • United States
  • United States Food and Drug Administration


  • Amines
  • Schiff Bases
  • Retinaldehyde