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Tong Li, Jingfa Zhang, Xiaodong Sun; The proteomic profiles in aqueous humor of patients with neovascular age-related macular degeneration.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5007.
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© ARVO (1962-2015); The Authors (2016-present)
To explore top-ranked aqueous humor proteins and identify specific biomarkers related to neovascular age-related macular degeneration (nAMD) and explore pathways related to neovascular AMD.
Eighteen nAMD patients initially treated with an intravitreal injection of Ranicizumab or Conbercept and ten age- and sex-matched cataract controls were studied.The proteome of 28 aqueous humor samples was analyzed by liquid chromatography coupled mass spectrometry. Then, label-free relative quantification of nAMD relative to cataract controls was performed. Application of a bioinformatics pipeline further analyzed the aqueous proteome by cluster and gene set enrichment analysis. A selection of differentially regulated proteins was validated by Western Blot and ELISA in a rat model of choroidal neovascularization.
A total of 837 proteins were identified in the aqueous of the nAMD group and quantified relatively to cataract controls. Different clusters of regulated proteins for each patient group were identified and showed characteristic enrichment of specific pathways including ‘‘PI3K-Akt signaling pathway’’ , ‘‘focal adhesion’’ and ‘‘complement and coagulation cascade’’ for nAMD patients. We identified myelin expression factor 2 (MYEF2) and regulating synaptic membrane exocytosis protein 2 (RIMS2) to be upregulated, while alpha-crystallin A chain (CRYAA) and telomere length regulation protein TEL2 (TELO2) to be downregulated in patients with nAMD. Additionally, RIMS2, MYEF2 protein expression levels were upregulated, while TELO2 and CRYAA protein expression levels were downregulated in a rat model of choroidal neovascularization.
The AH protein composition was significantly different between wet AMD and non-AMD patients. The described pathways specific for the nAMD patient groups and the identification of characteristic differentially regulated proteins provide a first step toward the definition of biomarkers for nAMD. The presented data will facilitate the investigation of mechanistic connections of proteins to the respective disease.
This is a 2020 ARVO Annual Meeting abstract.
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