TMT-based LC-MS/MS proteomics of vitreous from PDR versus MH/EMM control patients identified 59 DEPs, and PRM validation supported five candidate biomarkers (FV, PFN1, TXN, FTL, SeP) that may serve as potential candidate biomarkers for PDR.
Key Findings
Results
TMT combined with LC-MS/MS identified 4812 peptides and 877 proteins in vitreous samples from PDR patients and MH/EMM controls.
Discovery analysis compared vitreous from PDR patients with vitreous from macular hole (MH)/epimacular membrane (EMM) control patients.
Peptide and protein identification used tandem mass tag labeling with liquid chromatography-tandem mass spectrometry.
Results
59 differentially expressed proteins (DEPs) were identified between PDR and control vitreous.
DEP criteria were fold change > 1.2 and P < 0.05.
These DEPs indicate significant alterations in the vitreous protein profile of PDR patients.
Results
The DEPs were mainly involved in several core biological processes.
Enriched processes included cellular process, stimulus-response, biological regulation, localization, immune system process and metabolic process.
This was based on bioinformatics analysis of the DEPs.
Results
PRM validation successfully quantified 23 of 30 targeted proteins, and expression trends agreed overall with TMT quantification.
30 proteins with potential regulatory effects in PDR were selected for targeted parallel reaction monitoring (PRM) validation.
The overall expression trends were consistent between TMT-based quantification and PRM results.
Results
Five proteins (FV, PFN1, TXN, FTL, SeP) showed consistent trends and statistical significance in both discovery and validation cohorts.
The proteins are coagulation factor V, profilin-1, thioredoxin, ferritin light chain and selenoprotein P.
Each reached P < 0.05 in both the TMT discovery and PRM validation.
The authors suggest these may serve as potential candidate biomarkers and therapeutic targets for PDR.
What This Means
This study examined the proteins in the vitreous (the gel-like fluid inside the eye) of people with proliferative diabetic retinopathy (PDR), an advanced, sight-threatening diabetic eye disease. It compared them with proteins from patients with macular hole or epimacular membrane, who served as controls. Using mass spectrometry, the researchers identified 877 proteins and found 59 that differed between the groups.
The researchers then tested 30 proteins of interest with a second, targeted method. Twenty-three were successfully measured, and the results broadly matched the first analysis. Five proteins (coagulation factor V, profilin-1, thioredoxin, ferritin light chain and selenoprotein P) differed significantly in both the initial and validation analyses. Several of these relate to clotting, oxidative stress, and iron handling, though the abstract does not detail their specific roles.
This research suggests these five proteins could be candidates for future biomarker development and for studying how PDR develops. The findings are early-stage: they come from vitreous samples taken during eye surgery, and they do not show that these proteins can diagnose or treat PDR. Further studies would be needed to confirm their usefulness.
Xiong X, Zhou Q, Cao Y, Tang M, Xie L, Lv H. (2026). TMT-based quantitative proteomic analysis of vitreous humor in proliferative diabetic retinopathy.. BMC ophthalmology. https://doi.org/10.1186/s12886-026-04847-0