A2E‐Mediated Photochemical Modification to Fibronectin and its Implications to Age‐Related Changes in Bruch's Membrane

Abstract

Lipofuscin accumulates normally with age and is more pronounced in retinal dystrophies such as age-related macular degeneration. The major bis-retinoid component of lipofuscin is A2E. In addition to cell damage effects by A2E, we have previously demonstrated that blue-light-mediated A2E leads to modifications in the basement membrane protein laminin. Therefore, the purpose of this study was to advance the understanding of A2E photooxidation effects on fibronectin, the major glycoprotein of Bruch's membrane. In this study, A2E was irradiated with blue light in the presence of a fibronectin peptide consisting of amino acids from the integrin binding region. The modification sites were identified via LC/MS. Our research indicated that blue light irradiation caused cleavage throughout the A2E molecule closest to the pyridinium ring, and attached to the fibronectin peptide preferentially at lysine and arginine residues. All of these reactions are similar to the Maillard reaction. Altogether this study suggests that blue-light-irradiated A2E modifies peptides and forms advance glycation endproducts. Furthermore, these results can be used to identify modifications that occur in Bruch's membrane in vivo.