ArticleInvestigative ophthalmology & visual science2025
Effect of Pegcetacoplan on Aqueous Humor Proteome in Geographic Atrophy: A Prospective Exploration.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Pegcetacoplan, a complement component 3 (C3) inhibitor, has recently received U.S. Food and Drug Administration approval for treating geographic atrophy (GA), an advanced stage of age-related macular degeneration (AMD). However, the limited treatment response prompts further investigations into its molecular effects. Methods: We prospectively collected aqueous humor (AH) samples from 11 patients with GA before and at 2 months during pegcetacoplan treatment. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze the proteome, and global normalization was applied to account for differences in protein concentration. To assess global proteomic shifts over time, principal component analysis (PCA) was performed. The Friedman test was used to assess differences in protein intensities across time points while adjusting for multiple testing using Benjamini-Hochberg false discovery rate (FDR) correction. Results: A total of 283 proteins were analyzed. PCA revealed temporal changes in global protein expression profiles, with a significant shift between baseline and month 2 (P = 0.01). The levels of complement components C3 (P = 0.12) and C5 (P = 0.27) remained stable after initiation of treatment, but the levels of C1qB, C1RL, C2, C6, C7, C8, C9, factor D, factor H, and factor I increased significantly (all P < 0.05). Most non-complement proteins showed no significant changes; however, beta-2-glycoprotein 1 (FDR = 0.09), kininogen 1 (FDR < 0.05), and prothrombin (FDR < 0.05) increased significantly, and kallistatin (FDR < 0.05) and plasma serine protease inhibitor (FDR < 0.05) decreased. Conclusions: This exploratory study suggests that pegcetacoplan modulates the AH proteome in GA. Although no changes in the target protein C3 were detected following treatment, significant changes in proteins tightly connected to complement, inflammation, and coagulation were observed. These findings underscore the need for further investigation into the biological and clinical relevance of the observed molecular shifts.
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