Christian Schori1,2, Christian Trachsel3, Jonas Grossmann3, Ioanna Zygoula4, Daniel Barthelmes4,5, Christian Grimm1,2,6. 1. Lab for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Zurich, Switzerland. 2. Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. 3. Functional Genomics Center Zurich (FGCZ), ETH Zurich and University of Zurich, Zurich, Switzerland. 4. Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. 5. Save Sight Institute, The University of Sydney, Sydney, Australia. 6. Neuroscience Center Zurich (ZNZ), University of Zurich, Zurich, Switzerland.
Abstract
Purpose: In contrast to neovascular AMD (nAMD), no treatment option exists for dry AMD. Hence, the identification of specific biomarkers is required to facilitate diagnosis and therapy of dry AMD. Methods: The proteome of 34 vitreous humor samples (dry AMD: n = 6; nAMD: n = 10; proliferative diabetic retinopathy [PDR]: n = 9; epiretinal membrane [ERM]: n = 9) was analyzed by liquid chromatography coupled mass spectrometry. Then, label-free relative quantification of dry AMD, nAMD, and PDR relative to ERM, which was defined as the reference group, was performed. Application of a bioinformatics pipeline further analyzed the vitreous proteome by cluster and gene set enrichment analysis. A selection of differentially regulated proteins was validated by ELISA. Results: A total of 677 proteins were identified in the vitreous of the four patient groups and quantified relatively to ERM. Different clusters of regulated proteins for each patient group were identified and showed characteristic enrichment of specific pathways including "oxidative stress" for dry AMD, "focal adhesion" for nAMD, and "complement and coagulation cascade" for PDR patients. We identified cholinesterase (CHLE) to be specifically upregulated in dry AMD and ribonuclease (pancreatic; RNAS1) together with serine carboxypeptidase (probable; CPVL) to be upregulated in both forms of AMD. Conclusions: The described pathways specific for the different patient groups and the identification of characteristic differentially regulated proteins provide a first step toward the definition of biomarkers for dry AMD. The presented data will facilitate the investigation of mechanistic connections of proteins to the respective disease.
Purpose: In contrast to neovascular AMD (nAMD), no treatment option exists for dry AMD. Hence, the identification of specific biomarkers is required to facilitate diagnosis and therapy of dry AMD. Methods: The proteome of 34 vitreous humor samples (dry AMD: n = 6; nAMD: n = 10; proliferative diabetic retinopathy [PDR]: n = 9; epiretinal membrane [ERM]: n = 9) was analyzed by liquid chromatography coupled mass spectrometry. Then, label-free relative quantification of dry AMD, nAMD, and PDR relative to ERM, which was defined as the reference group, was performed. Application of a bioinformatics pipeline further analyzed the vitreous proteome by cluster and gene set enrichment analysis. A selection of differentially regulated proteins was validated by ELISA. Results: A total of 677 proteins were identified in the vitreous of the four patient groups and quantified relatively to ERM. Different clusters of regulated proteins for each patient group were identified and showed characteristic enrichment of specific pathways including "oxidative stress" for dry AMD, "focal adhesion" for nAMD, and "complement and coagulation cascade" for PDR patients. We identified cholinesterase (CHLE) to be specifically upregulated in dry AMD and ribonuclease (pancreatic; RNAS1) together with serine carboxypeptidase (probable; CPVL) to be upregulated in both forms of AMD. Conclusions: The described pathways specific for the different patient groups and the identification of characteristic differentially regulated proteins provide a first step toward the definition of biomarkers for dry AMD. The presented data will facilitate the investigation of mechanistic connections of proteins to the respective disease.
Authors: Gabriel Velez; Jing Yang; Angela S Li; Stephen H Tsang; Alexander G Bassuk; Vinit B Mahajan Journal: Sci Rep Date: 2019-05-20 Impact factor: 4.379
Authors: Sarah R Weber; Yuanjun Zhao; Christopher Gates; Jingqun Ma; Felipe da Veiga Leprevost; Venkatesha Basrur; Alexey I Nesvizhskii; Thomas W Gardner; Jeffrey M Sundstrom Journal: J Clin Med Date: 2021-05-25 Impact factor: 4.241