Increase in the advanced glycation end product pentosidine in Bruch's membrane with age

PURPOSE. To determine whether there is an age-related increase of pentosidi ne in human Bruch's membranes and to localize pentosidine and carboxymethyl lysine (CML), two well-characterized, advanced glycation end products (AGEs ) in aged human Bruch's membranes and choroid in vivo. METHODS. Human Bruch's membrane samples were isolated from the retinal pigm ent epithelium (RPE) and choroid and subjected to reversed-phase high-perfo rmance liquid chromatography to determine pentosidine content. A polyclonal anti-pentosidine antibody and a monoclonal antibody specific for carboxyme thyllysine were used to localize AGEs in 20-month-old nondiabetic, 82-year- old nondiabetic, and 82-year-old diabetic globes. RESULTS. Human Bruch's membranes (n = 20) showed a linear age-dependent inc rease in pentosidine that reached approximately 0.17 millimoles pentosidine per mole hp droxyproline in late life (r = 0.896; P < 0.001). Immunohistoc hemical evaluation showed evidence of pentosidine in Bruch's membrane, chor oidal extracellular matrix, and vessel walls in the 82-year-old nondiabetic and diabetic globes. A similar staining pattern was found with the anti-CM L antibody. Basal laminar deposits and drusen stained with both antibodies in the elderly nondiabetic eye. In contrast, neither antibody stained the 2 0-month-old tissue. CONCLUSIONS. We provide biochemical and immunohistochemical evidence for th e formation of pentosidine and CML structures in human Bruch's membrane and choroid with age. These changes could promote aging of the RPE-Bruch's mem brane-choroid complex.