Pre-Treatment with Pyridoxamine Mitigates Isolevuglandin-Associated Retinal Effects in Mice Exposed to Bright Light.

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TitlePre-Treatment with Pyridoxamine Mitigates Isolevuglandin-Associated Retinal Effects in Mice Exposed to Bright Light.
Publication TypeJournal Article
Year of Publication2013
AuthorsCharvet, CDouglas, Saadane, A, Wang, M, Salomon, RG, Brunengraber, H, Turko, IV, Pikuleva, IA
JournalJ Biol Chem
Date Published2013 Aug 22
ISSN1083-351X
Abstract

The benefits of antioxidant therapy for treating age-related macular degeneration, a devastating retinal disease, are limited. Perhaps species other than reactive oxygen intermediates should be considered as therapeutic targets. These could be lipid peroxidation products, including isolevuglandins (isoLGs), prototypical and extraordinarily reactive γ-ketoaldehydes that avidly bind to proteins, phospholipids, and DNA and modulate the properties of these biomolecules. We found IsoLG adducts in aged human retina but not in the retina of mice kept under dim lighting. Hence, to test whether scavenging of isoLGs could complement or supplant antioxidant therapy, we exposed mice to bright light and found that this insult leads to retinal isoLG-adduct formation. We then pre-treated mice with pyridoxamine - a B6 vitamer and efficient scavenger of γ-ketoaldehydes - and found that the levels of retinal isoLG adducts are decreased and morphological changes in photoreceptor mitochondria are not as pronounced as in untreated animals. Our study demonstrates that preventing the damage to biomolecules by lipid peroxidation products, a novel concept in vision research, is a viable strategy to combat oxidative stress in the retina.

DOI10.1074/jbc.M113.498832
Alternate JournalJ. Biol. Chem.
PubMed ID23970548