Serum Amyloid A 4 as a Common Marker of Persistent Inflammation in Patients with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

J Inflamm Res. 2023 Aug 29:16:3783-3797. doi: 10.2147/JIR.S417791. eCollection 2023.

Abstract

Background: Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV.

Methods: Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis.

Results: A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls.

Conclusion: This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.

Keywords: inflammation; neovascular age-related macular degeneration; polypoidal choroidal vasculopathy; serum amyloid A 4.

Grants and funding

The study was supported by National Natural Science Foundation of China (82171085); Key Project of Internet Cross-Border Integration Innovation and Technology of Tianjin (18ZXRHSY00210); Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-037A); Science and Technology Project of Tianjin Binhai New Area Health Commission (2022BWKQ011); the Natural Science Foundation of Tianjin City (22JCQNJC01220).