Back to Search Start Over

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

Authors :
Steffen E. Künzel
Leonie T. M. Flesch
Dominik P. Frentzel
Vitus A. Knecht
Anne Rübsam
Felix Dreher
Moritz Schütte
Alexandre Dubrac
Bodo Lange
Marie-Laure Yaspo
Hans Lehrach
Antonia M. Joussen
Oliver Zeitz
Source :
International Journal of Molecular Sciences, Vol 24, Iss 12, p 10327 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
24
Issue :
12
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.14b4714459fe45a5b1d405d4c6e5baac
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms241210327