Proteomic Profiles in Advanced Age-related Macular Degeneration Using an Aptamer-based Proteomic Technology

Abstract

Purpose : To: 1) identify top-ranked proteins related to neovascular (NV) Age-related Macular Degeneration (AMD) and geographic atrophy (GA), and 2) identify pathways related to NV-AMD and GA.

Methods : We conducted a pilot study of patients with neovascular (NV)-AMD (n = 10), GA (n = 10), and age-matched cataract controls (n = 10) who were recruited into an AMD registry. We measured 4001 plasma proteins using an aptamer-based proteomic technology. Concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of NV-AMD versus controls and between cases of GA versus controls using linear regression. Top-ranked proteins were defined as a protein with an unadjusted p-value <0.001, corresponding to a conservative Bonferroni adjustment for multiple comparisons. Pathway analysis was conducted using pathways downloaded from Reactome, and a functional class scoring approach using the p-values as the protein-level statistics..

Results : Higher levels of vinculin (actin filament -binding protein involved in cell-matrix adhesion and cell-cell adhesion) and lower levels of CD177 (neutrophil cell surface receptor) levels were found in patients with NV-AMD compared with controls (Figure 1). Pro-neuregulin-4 (low affinity ligand for the ErbB4 tyrosine kinase receptor) was higher in cases of GA compared with controls and soluble inter-cellular adhesion molecule-1 (an intra-cellular adhesion molecule) was lower in patients with GA compared with controls (Figure 2). For NV-AMD, cargo trafficking to the periciliary membrane and vascular endothelial growth factor (VEGF) - related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling.

Conclusions : We found two different pathways and different proteins in patients with the NV and GA phenotypes of advanced AMD. Vinculin, had previously been described as having a role in AMD. Some of the top ranked pathways have also been previously associated with AMD, providing some assurance of the results and the novel proteins identified by this technology. Biomarkers identified using this technique reflect systemic alterations in plasma proteins, which may improve our understanding of the mechanism of AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1. Differences in Group Means in Cases of NV-AMD Compared with Controls

 

Figure 2. Differences in Group Means in Cases of GA Compared with Controls