Abstract
Purpose :
Current treatment of uveitis mainly involves corticosteroids that can have therapy-limiting side effects including secondary glaucoma and cataract. We hypothesize that our multi-omics tool TEMPO (Tracing Expression of Multiple Protein Origins) allows to uncover disease mechanisms in living patients that may lead to improved diagnostics and alternative immunosuppressive therapies.
Methods :
Aqueous humor liquid biopsies were collected from 6 patients with uveitis and from 19 control patients undergoing cataract surgery. TEMPO integrates high-resolution proteomics of 50µL-liquid biopsies with cell level transcriptomics from 82,072 cells from 72 different cell types in tissues of the human eye.
Results :
We identified 5,953 unique proteins in aqueous humor liquid biopsies. TEMPO revealed specific protein signatures originating from various immune cell types, including neutrophils (e.g. MMP9, MPO), hyalocytes (e.g. CXCL10, CCL22), B cells (e.g. IGHM, IGHD), and T cells (e.g. GNLY, CD8A). We also found a significant increase of marker proteins of vascular endothelial cells (e.g. TIE1, ANGPT2) and liver-specific proteins (e.g. APOA1, F7), findings that may correspond to vascular inflammation and leakage, as seen in uveitis patients. When looking at downregulated proteins in uveitis, the marker proteins of cones (e.g. BICDL1, FGF23) and amacrine cells (e.g. CPNE7, TYRO3) were most significantly decreased, an indicator of molecular retinal damage.
Conclusions :
TEMPO identified almost 6000 different proteins in 50µL aqueous humor liquid biopsies and detected cell type-specific protein signatures that enable cell level analyses in living humans. Our findings may lead to improved diagnostic phenotyping and novel immunosuppressive therapies for patients with uveitis.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.