Liquid Biopsy Proteomics in Ophthalmology

Abstract

Minimally invasive liquid biopsies from the eye capture locally enriched fluids that contain thousands of proteins from highly specialized ocular cell types, presenting a promising alternative to solid tissue biopsies. The advantages of liquid biopsies include sampling the eye without causing irreversible functional damage, potentially better reflecting tissue heterogeneity, collecting samples in an outpatient setting, monitoring therapeutic response with sequential sampling, and even allowing examination of disease mechanisms at the cell level in living humans, an approach that we refer to as TEMPO (Tracing Expression of Multiple Protein Origins). Liquid biopsy proteomics has the potential to transform molecular diagnostics and prognostics and to assess disease mechanisms and personalized therapeutic strategies in individual patients. This review addresses opportunities, challenges, and future directions of high-resolution liquid biopsy proteomics in ophthalmology, with particular emphasis on the large-scale collection of high-quality samples, cutting edge proteomics technology, and artificial intelligence-supported data analysis.

Advances in aqueous humor proteomics for biomarker discovery and disease mechanisms exploration: a spotlight on primary open angle glaucoma

“…Functionally, AH proteins are mainly involved in immune response, inflammation, coagulation as well as energy metabolism ( Yu et al, 2020 ), and it is considered strongly influenced by sex and ethnicity ( Perumal et al, 2017 ; Haq et al, 2021 ; Vashishtha et al, 2023 ). General challenges in ocular liquid proteomics have recently been reviewed ( Wolf et al, 2024 ).…”

“…This represents a significant improvement in analysis depth as compared to existing LC-MS/MS approaches. It is noteworthy, that the target menu of SomaScan v4.1 lacks coverage of various eye specific targets ( Wolf et al, 2024 ), rendering likely an even higher number of protein detections from the sample type when subjected to the novel 11k panel.…”

Integrating the analysis of human biopsies using post‐translational modifications proteomics

“…However, such biofluids can be challenging to analyze due to high dynamic ranges of proteins. To address this issue and better characterize protein levels abundance, a new data integration approach called TEMPO or T racing E xpression of M ultiple P rotein O rigins (Wolf et al, 2023 ; Wolf et al, 2024 ). Using TEMPO, a high‐resolution proteomic profiling of aqueous and vitreous humor from 120 living patients was performed using a DNA aptamer‐based proteomics approach (SomaLogic) to quantify >5,900 proteins (Wolf et al, 2023 ).…”