Proteomic Analysis of the Aqueous Humor in Age-related Macular Degeneration (AMD) Patients

Age-related macular degeneration (AMD) can lead to irreversible
central vision loss in the elderly. Although large number of growth
factor pathways, including the vascular endothelial growth factor
(VEGF), has been implicated in the pathogenesis of AMD, no study has
directly assessed the whole proteomic composition in the aqueous humor
(AH) among AMD patients. The AH contains proteins secreted from the
anterior segment tissue, and these proteins may play an important
role in the pathogenesis of AMD. Thus, comparisons between the AH
proteomic profiles of AMD patients and non-AMD controls may lead to
the verification of novel pathogenic proteins useful as potential
clinical biomarkers. In this study, we used discovery-based proteomics
and Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) to analyze
AH from AMD patients and AH from controls who underwent cataract surgery.
A total of 154 proteins with at least two unique peptides were identified
in the AH. Of these 154 proteins identified by discovery-based proteomics,
10 AH proteins were novel identifications. The protein composition
in the AH was different between AMD patients and non-AMD controls.
Subsequently, a systematic MRM-MS assay was performed in seven highly
abundant differentially expressed proteins from these groups. Differential
expression of three proteins was observed in the AH of AMD patients
compared with that of cataract controls (p < 0.0312).
Elucidation of the aqueous proteome will establish a foundation for
protein function analysis and identify differentially expressed markers
associated with AMD. This study demonstrates that integrated proteomic
technologies can yield novel biomarkers to detect exudative AMD.