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

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:

• serum amyloid A 4
• inflammation
• neovascular age-related macular degeneration
• polypoidal choroidal vasculopathy

Data Sharing Statement

The data presented in this study are available on request from the corresponding author.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No. 2021KY-12).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

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).