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Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis

Although complement inhibition has emerged as a possible therapeutic strategy for age-related macular degeneration (AMD), there is not a clear consensus regarding what aspects of the complement pathway are dysregulated in AMD and when this occurs relative to disease stage. We recently published a sy...

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Detalles Bibliográficos
Autores principales: Lin, Jonathan B., Serghiou, Stylianos, Miller, Joan W., Vavvas, Demetrios G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105289/
https://www.ncbi.nlm.nih.gov/pubmed/35566495
http://dx.doi.org/10.3390/jcm11092371
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author Lin, Jonathan B.
Serghiou, Stylianos
Miller, Joan W.
Vavvas, Demetrios G.
author_facet Lin, Jonathan B.
Serghiou, Stylianos
Miller, Joan W.
Vavvas, Demetrios G.
author_sort Lin, Jonathan B.
collection PubMed
description Although complement inhibition has emerged as a possible therapeutic strategy for age-related macular degeneration (AMD), there is not a clear consensus regarding what aspects of the complement pathway are dysregulated in AMD and when this occurs relative to disease stage. We recently published a systematic review describing systemic complement activation profiles in patients with early/intermediate AMD or geographic atrophy (GA) compared to non-AMD controls. Here, we sought to meta-analyze these results to estimate the magnitude of complement dysregulation in AMD using restricted maximum likelihood estimation. The seven meta-analyzed studies included 710 independent participants with 23 effect sizes. Compared with non-AMD controls, patients with early/intermediate nonexudative AMD (N = 246) had significantly higher systemic complement activation, as quantified by the levels of complement proteins generated by common final pathway activation, and significantly lower systemic complement inhibition. In contrast, there were no statistically significant differences in the systemic levels of complement common final pathway activation products or complement inhibition in patients with GA (N = 178) versus non-AMD controls. We provide evidence that systemic complement over-activation is a feature of early/intermediate nonexudative AMD; no such evidence was identified for patients with GA. These findings provide mechanistic insights and inform future clinical trials.
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spelling pubmed-91052892022-05-14 Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis Lin, Jonathan B. Serghiou, Stylianos Miller, Joan W. Vavvas, Demetrios G. J Clin Med Article Although complement inhibition has emerged as a possible therapeutic strategy for age-related macular degeneration (AMD), there is not a clear consensus regarding what aspects of the complement pathway are dysregulated in AMD and when this occurs relative to disease stage. We recently published a systematic review describing systemic complement activation profiles in patients with early/intermediate AMD or geographic atrophy (GA) compared to non-AMD controls. Here, we sought to meta-analyze these results to estimate the magnitude of complement dysregulation in AMD using restricted maximum likelihood estimation. The seven meta-analyzed studies included 710 independent participants with 23 effect sizes. Compared with non-AMD controls, patients with early/intermediate nonexudative AMD (N = 246) had significantly higher systemic complement activation, as quantified by the levels of complement proteins generated by common final pathway activation, and significantly lower systemic complement inhibition. In contrast, there were no statistically significant differences in the systemic levels of complement common final pathway activation products or complement inhibition in patients with GA (N = 178) versus non-AMD controls. We provide evidence that systemic complement over-activation is a feature of early/intermediate nonexudative AMD; no such evidence was identified for patients with GA. These findings provide mechanistic insights and inform future clinical trials. MDPI 2022-04-23 /pmc/articles/PMC9105289/ /pubmed/35566495 http://dx.doi.org/10.3390/jcm11092371 Text en © 2022 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
Lin, Jonathan B.
Serghiou, Stylianos
Miller, Joan W.
Vavvas, Demetrios G.
Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis
title Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis
title_full Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis
title_fullStr Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis
title_full_unstemmed Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis
title_short Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis
title_sort systemic complement activation profiles in nonexudative age-related macular degeneration: a meta-analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105289/
https://www.ncbi.nlm.nih.gov/pubmed/35566495
http://dx.doi.org/10.3390/jcm11092371
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