Carboxymethyl-lysine-modified plasma proteins in age-related macular degeneration

To identify increased or decreased levels of carboxymethyl lysine (CML)-modified proteins in the plasma of age-related macular degeneration (AMD) patients and age-matched controls for the identification of possible plasma biomarkers of AMD and its progression. Plasma samples from patients with wet AMD with choroidal neovascularization (wAMD group) (n = 10), intermediate dry AMD (dAMD group) (n = 10), and age-matched controls (control group) (n = 10) were immunoprecipitated to select peptides with CML modification. LC-MS/MS was used to identify proteins in each group with CML modification. Among the identified CML enriched proteins, 6 commonly abundant proteins were identified in the plasma. There was no significant difference in amount of these proteins among the three groups, except CML-modified albumin, which was significantly decreased with progressed AMD (P = 0.0015). Five proteins were identified in the control group only, and 10 other proteins were identified in the dAMD group, and 4 other proteins in the wAMD group. Proteins involved in inflammatory responses and immunologic response were found to contain CML in the less advanced dAMD group. In the more advanced wAMD group, intracellular proteins associated with transcription or molecular activation associated with angiogenesis or blood vessel formation were found to be altered with CML. Proteins involved in inflammatory and immunologic response were CML-modified in earlier dry AMD while proteins associated with angiogenesis and blood vessel formation were CML-modified in advanced wet AMD, suggesting the possible role of oxidative change of proteins with different functions as the pathophysiology of the development and progression of AMD.