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Itay Chowers, Gala Beykin, Liran Tiosano, Samer Khateb, Sarah Hayoun, Michelle Grunin, Shira Levi, Batya Rinsky; Analysis of the Aqueous Humor Proteome in Patients with Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):356.
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Age-related macular degeneration (AMD) is associated with marked altered gene and protein expression in the retina. We wished to characterize the aqueous humor (AH) proteome in AMD patients in order to gain insight into the pathogenesis of the disease and identify potential biomarkers.
AH was collected during cataract surgery from 10 neovascular AMD (nvAMD) patients (mean age 81.8±5.69, Female/Male =5/5) and 10 age-matched controls (mean age 78.3±6.22, Female/Male =5/5). AH was pooled together to create two samples (nvAMD and controls), followed by intensity-based label-free quantification (MS1). Functional analysis was performed via DAVID 6.8. A validation set [20 controls (mean age 74.8±7.14, Female/ Male=10/10), 15 atrophic AMD (aAMD) (mean age 77.3±10.47, Female/Male=5/10) and 15 nvAMD (mean age78.6±7.45, Female/Male=9/6)] was tested via multiplex ELISA for 9 proteins that were differentially expressed in nvAMD.
A total of 674 proteins were identified in AH by MS1. 239 proteins were upregulated in nvAMD (nvAMD/Control>2, peptide tags>2), and 86 proteins were upregulated in controls (nvAMD/Control<0.5, peptide tags>2). Functional analysis demonstrated enrichment for platelet degranulation (enrichment score (ES): 28.1), negative regulation of endopeptidase activity (ES: 18.82), cellular protein metabolic process (ES: 11.78), Epidermal growth factor-like domain (ES: 10.34), Sushi/SCR/CCP (ES: 10.14) and complement and coagulation cascades (ES: 9.16). AMD proteins expressed were upregulated for 3/6 protein clusters (χ2<0.05 compared to randomized data). Multiplex ELISA on the validation set confirmed the MS1 results in 3/9 proteins tested (p<0.05).
Comparison between the AH proteomic profiles of AMD patients in different stages of the disease and controls provide insight as to the pathogenesis of AMD. Several proteins and functional classes show altered expression in AH from AMD patients. Further research should confirm if these proteins may serve as biomarkers of AMD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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