Systematic Review of Proteomics in Age-Related Macular Degeneration and Pathway Analysis of Significant Protein Changes

Abstract

Topic

Proteomics in age-related macular degeneration (AMD) research.

Clinical Relevance

AMD is the leading cause of blindness in industrialized countries, with a poorly understood pathogenesis. Proteomics can identify significantly altered proteins in AMD patients, aiding in understanding the disease’s pathophysiology and potentially improving diagnosis or treatment strategies.

Methods

A systematic review of proteomic studies in AMD was conducted. Proteins significantly altered in dry and wet AMD and those tested as biomarkers were presented according to sample type (aqueous humor, plasma, urine, vitreous, retinal pigment epithelium/choroid, and tear film) and type of assay (mass spectrometry or aptamers) used in the individual studies. Proteins that exhibited at least a 2× fold change (FC) were further analyzed through functional enrichment analysis and protein–protein interaction networks (STRING database).

Results

Twenty-two studies (case-control and cohorts) with a total of 6932 participants were included. The included studies showed significant heterogeneity, and most of them lacked sufficient power. Results suggested that various proteins and pathways are implicated in AMD, and there were differences when comparing results from the individual studies and unbiased results. Although many proteins differed significantly between AMD and control groups, most exhibited less than a 2-FC. Functional analysis of proteins with ≥|2|-FCs (identified by unbiased proteomics in multiple biofluids) highlighted lipid metabolism and protease regulation pathways as central to both dry and wet AMD. Complement and coagulation cascades, chaperones, and glycolysis pathways were significant in wet AMD, whereas matrix remodeling pathways were enriched mostly in dry AMD.

Conclusion

Combining proteomics from various studies could reveal new protein–protein interaction networks and associated functional pathways that may suggest novel potential therapeutic targets for AMD. However, there is a scarcity of data available for early AMD from ocular biofluids, and it should be the aim of future proteomics studies.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.