High-Dimensional Vitreous Proteomics Identifies Epigenetic Pathway Signatures in Vitreoretinal Lymphoma.

Authors

Jun Funatsu, Nobuyo Yawata, Satoko Nakano, Yuki Asahara, Koh-Hei Sonoda, Atsunobu Takeda

Published in

Ophthalmology science. Volume 6. Issue 9. Pages 101317. Epub Jul 06, 2026.

Abstract

In this study, we sought to characterize systems-level vitreous proteomic alterations associated with vitreoretinal lymphoma (VRL) and determine whether coordinated proteomic signatures associated with diffuse large B-cell lymphoma (DLBCL) biology are detectable within the intraocular microenvironment.
A cross-sectional observational study.
We included 11 immunocompetent patients diagnosed with VRL (DLBCL subtype) and 4 patients with a macular hole to serve as the noninflammatory controls.
Undiluted vitreous samples from 11 eyes with VRL and 4 control eyes were analyzed using the SomaScan 7K aptamer‑based proteomic platform (SomaLogic), enabling quantification of 6981 proteins from limited-volume specimens. Differential expression analysis was performed using empirical Bayes linear modeling with false discovery rate (FDR) correction, followed by Gene Ontology, Reactome, and gene set enrichment analyses.
Differentially expressed vitreous proteins and enriched biological pathways in VRL and control samples.
Unbiased proteomic profiling revealed a distinct molecular signature in VRL vitreous samples, characterized by a coordinated enrichment of proteins associated with nuclear and chromatin-related pathways. A total of 2499 proteins met the predefined differential expression criteria (|log2-fold change| ≥ 0.5; adjusted P < 0.10), including 2440 upregulated and 59 downregulated proteins in VRL. Unsupervised analyses demonstrated a clear separation between the groups. Across complementary analyses, VRL showed enrichment of proteins associated with nuclear, chromatin-related, and epigenetic regulatory pathways, including deoxyribonucleic acid methylation, polycomb repressive complex-2‑mediated histone modification, histone deacetylation, and cell cycle-related transcriptional regulation. In parallel, pathways related to extracellular matrix organization, vesicle-associated components, and growth factor signaling were relatively reduced. Gene set enrichment analyses supported enrichment of nuclear regulatory pathway signatures (FDR <0.05).
Vitreoretinal lymphoma was characterized by enrichment of proteins associated with nuclear and epigenetic regulatory pathways and the relative suppression of extracellular structural pathways, suggesting substantial intraocular microenvironmental remodeling. These findings demonstrate that high-dimensional vitreous proteomics can capture proteomic features associated with lymphoma-related pathways and provide a framework for molecular characterization and biomarker discovery in intraocular lymphoma.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PMID:
42568936
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.