Positive progress reported in search for AMD biomarkers

Early experience with peptidomic profiling of plasma for age-related macular degeneration (AMD) biomarkers is encouraging in suggesting this technique may some day have a role in the identification of individuals susceptible to developing this vision-threatening disorder, said John W. Crabb, PhD.

Dr. Crabb and colleagues at the Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, analyzed peptidomic patterns in blood samples obtained from patients with AMD and normal controls using anti-carboxyethylpyrrole (CEP) immunoaffinity plasma fractionation and MALDI TOF mass spectrometry.

Their focus on identifying peptides with CEP adducts was based on previous research that showed CEP adducts were elevated in ocular tissues and plasma of patients with AMD compared with normal controls and able to induce new blood vessel growth in a rat cornea model. Those findings led to the hypothesis that the CEP adducts, which are oxidative protein modifications, serve as a primary catalyst in AMD pathology and are causally involved in drusen formation, Bruch's membrane thickening, choroidal neovascularization, and activation of the immune response.

Comparisons of plasma from the patients with AMD and controls led to the identification of 222 peptides that were significantly different between the two populations. A cross-validation study investigating the performance of the peptidomic pattern analysis was conducted using blood collected from 90 patients with AMD and 80 normal donors and demonstrated accuracy of 94% by correctly identifying 159 of the 170 samples.

"Plasma contains about 5,000 peptides that are derived as proteolytic degradation products of tissues throughout the body," Dr. Crabb said. "The idea of peptidomic profiling is to sort through the peptides and find the ones that reflect the tissue of interest in order to monitor its health.

"Work is now ongoing to characterize the structure of the peptides we've identified as associated with AMD," he continued. "In the future, true validation of the potential prognostic utility of this approach will require identification and follow-up of AMD-susceptible candidates."