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.
Department of Ophthalmology, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
Tae Wan
TW
Kim
Jeong Won
JW
Kang
Jeeyun
J
Ahn
Eun Kyung
EK
Lee
Kyung-Cho
KC
Cho
Bit Na Ra
BN
Han
Nam Young
NY
Hong
Jisook
J
Park
Kwang Pyo
KP
Kim
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001082:Aqueous Humor / Q000378:metabolism*; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D012372:ROC Curve; D015203:Reproducibility of Results
D015415:Biomarkers; D005136:Eye Proteins; D010446:Peptide Fragments; D020543:Proteome