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Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration

There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncov...

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Autores principales: Künzel, Steffen E., Flesch, Leonie T. M., Frentzel, Dominik P., Knecht, Vitus A., Rübsam, Anne, Dreher, Felix, Schütte, Moritz, Dubrac, Alexandre, Lange, Bodo, Yaspo, Marie-Laure, Lehrach, Hans, Joussen, Antonia M., Zeitz, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299094/
https://www.ncbi.nlm.nih.gov/pubmed/37373474
http://dx.doi.org/10.3390/ijms241210327
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author Künzel, Steffen E.
Flesch, Leonie T. M.
Frentzel, Dominik P.
Knecht, Vitus A.
Rübsam, Anne
Dreher, Felix
Schütte, Moritz
Dubrac, Alexandre
Lange, Bodo
Yaspo, Marie-Laure
Lehrach, Hans
Joussen, Antonia M.
Zeitz, Oliver
author_facet Künzel, Steffen E.
Flesch, Leonie T. M.
Frentzel, Dominik P.
Knecht, Vitus A.
Rübsam, Anne
Dreher, Felix
Schütte, Moritz
Dubrac, Alexandre
Lange, Bodo
Yaspo, Marie-Laure
Lehrach, Hans
Joussen, Antonia M.
Zeitz, Oliver
author_sort Künzel, Steffen E.
collection PubMed
description There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient’s level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD.
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spelling pubmed-102990942023-06-28 Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration Künzel, Steffen E. Flesch, Leonie T. M. Frentzel, Dominik P. Knecht, Vitus A. Rübsam, Anne Dreher, Felix Schütte, Moritz Dubrac, Alexandre Lange, Bodo Yaspo, Marie-Laure Lehrach, Hans Joussen, Antonia M. Zeitz, Oliver Int J Mol Sci Article There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient’s level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD. MDPI 2023-06-19 /pmc/articles/PMC10299094/ /pubmed/37373474 http://dx.doi.org/10.3390/ijms241210327 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Künzel, Steffen E.
Flesch, Leonie T. M.
Frentzel, Dominik P.
Knecht, Vitus A.
Rübsam, Anne
Dreher, Felix
Schütte, Moritz
Dubrac, Alexandre
Lange, Bodo
Yaspo, Marie-Laure
Lehrach, Hans
Joussen, Antonia M.
Zeitz, Oliver
Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration
title Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration
title_full Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration
title_fullStr Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration
title_full_unstemmed Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration
title_short Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration
title_sort systemic blood proteome patterns reflect disease phenotypes in neovascular age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299094/
https://www.ncbi.nlm.nih.gov/pubmed/37373474
http://dx.doi.org/10.3390/ijms241210327
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