Primary amines protect against retinal degeneration in mouse models of retinopathies

Akiko Maeda, Marcin Golczak, Yu Chen, Kiichiro Okano, Hideo Kohno, Satomi Shiose, Kaede Ishikawa, William Harte, Grazyna Palczewska, Tadao Maeda, Krzysztof Palczewski

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89 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)170-178
Number of pages9
JournalNature Chemical Biology
Volume8
Issue number2
DOIs
Publication statusPublished - Feb 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Maeda, A., Golczak, M., Chen, Y., Okano, K., Kohno, H., Shiose, S., Ishikawa, K., Harte, W., Palczewska, G., Maeda, T., & Palczewski, K. (2012). Primary amines protect against retinal degeneration in mouse models of retinopathies. Nature Chemical Biology, 8(2), 170-178. https://doi.org/10.1038/nchembio.759