Pretreatment with Pyridoxamine Mitigates Isolevuglandinassociated Retinal Effects in Mice Exposed to Bright Light
Casey Charvet, Aicha Saadane, Meiyao M. Wang, Robert Salomon, Henri Brunengraber, Christine Curcio, Illarion Turko, Irina Pikuleva
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.
The Journal of Biological Chemistry
B6 vitamer, lipid peroxidation, multiple reaction monitoring, mass spectrometry
, Saadane, A.
, Wang, M.
, Salomon, R.
, Brunengraber, H.
, Curcio, C.
, Turko, I.
and Pikuleva, I.
Pretreatment with Pyridoxamine Mitigates Isolevuglandinassociated Retinal Effects in Mice Exposed to Bright Light, The Journal of Biological Chemistry
(Accessed February 21, 2024)