Pretreatment with Pyridoxamine Mitigates Isolevuglandinassociated Retinal Effects in Mice Exposed to Bright Light

Published

October 11, 2013

Author(s)

Casey Charvet, Aicha Saadane, Meiyao M. Wang, Robert Salomon, Henri Brunengraber, Christine Curcio, Illarion Turko, Irina Pikuleva

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 -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 isoLGadduct formation.Wethen pretreated mice with pyridoxamine, a B6 vitamer and efficient scavenger of -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.

Citation

The Journal of Biological Chemistry

Volume

288

Issue

41

Pub Type

Journals

Keywords

B6 vitamer, lipid peroxidation, multiple reaction monitoring, mass spectrometry

Citation

Charvet, C. , Saadane, A. , Wang, M. , Salomon, R. , Brunengraber, H. , Curcio, C. , Turko, I. and Pikuleva, I. (2013), Pretreatment with Pyridoxamine Mitigates Isolevuglandinassociated Retinal Effects in Mice Exposed to Bright Light, The Journal of Biological Chemistry (Accessed May 5, 2024)