This study identifies stratifin (SFN) and hornerin (HRNR) as systemic candidate biomarkers reflecting microvascular alterations in diabetic retinopathy, with serum SFN levels significantly increased in DR versus T2DM and serum HRNR levels significantly decreased in DR with diabetic nephropathy compared with T2DM.
Key Findings
Results
Proteomic analysis of fibrovascular membrane tissue identified 44 FVM-specific proteins compared to normal retinal vasculature.
Human retinal vasculature from non-diabetic donors and FVM tissues from PDR patients undergoing pars plana vitrectomy (PPV) were analyzed by one-dimensional liquid chromatography-mass spectrometry.
Among the 44 FVM-specific proteins identified, stratifin (SFN) and hornerin (HRNR) were notably linked to retinal angiogenesis.
Functional enrichment and protein interaction analyses were performed using STRING databases.
FVM represents a pathological tissue causing retinal traction and is an advanced stage of proliferative diabetic retinopathy (PDR).
Results
Serum SFN levels were significantly increased in DR patients compared to T2DM patients.
Serum levels of SFN were measured by ELISA in T2DM, DR, and DR with diabetic nephropathy (DR with DN) cohorts.
ROC analyses demonstrated acceptable accuracy for differentiating DR stages based on serum SFN levels.
SFN was identified as one of the FVM-specific proteins linked to retinal angiogenesis.
This is described as the first study to identify SFN as a systemic candidate biomarker reflecting microvascular alterations in DR.
Results
Serum HRNR levels were significantly decreased in DR with diabetic nephropathy (DR with DN) compared to T2DM patients.
Serum levels of HRNR were measured by ELISA in T2DM, DR, and DR with DN cohorts.
ROC analyses demonstrated acceptable accuracy for differentiating DR stages based on serum HRNR levels.
HRNR was identified as one of the FVM-specific proteins linked to retinal angiogenesis.
This is described as the first study to identify HRNR as a systemic candidate biomarker reflecting microvascular alterations in DR.
Results
Messenger RNA expression of selected proteins was quantified in peripheral blood mononuclear cells (PBMCs) across healthy, T2DM, and DR with nephropathy patient groups.
mRNA expression was quantified by quantitative PCR (qPCR) in peripheral blood mononuclear cells from healthy, T2DM, and DR with DN patients.
The PBMC expression analysis complemented the serum ELISA measurements for SFN and HRNR.
Three patient cohorts were included: healthy controls, T2DM, and DR with DN.
Results
ROC curve analyses demonstrated acceptable diagnostic accuracy for both SFN and HRNR in differentiating stages of diabetic retinopathy.
Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance of serum SFN and HRNR levels.
ROC analyses demonstrated 'acceptable accuracy for differentiating DR stages based on serum SFN and HRNR levels.'
The diagnostic evaluation spanned multiple disease stages including T2DM, DR, and DR with DN.
The authors note that larger cohort studies are warranted to validate clinical relevance for early detection and therapeutic targeting of DR.
What This Means
This research suggests that two proteins — stratifin (SFN) and hornerin (HRNR) — found in abnormal scar tissue that forms in the eyes of people with advanced diabetic eye disease may also be detectable in the blood, potentially serving as indicators of diabetic retinopathy (DR) at various stages. The researchers first identified these proteins by comparing the molecular makeup of pathological retinal tissue from patients with severe diabetic eye disease to normal retinal blood vessel tissue from non-diabetic donors. They then measured these proteins in the blood of patients with type 2 diabetes at different stages of disease, including those who also had kidney disease.
The study found that blood levels of SFN were higher in patients with diabetic retinopathy compared to those with diabetes alone, while HRNR levels were lower in patients who had both diabetic retinopathy and kidney disease. Statistical tests showed that these blood protein levels had acceptable ability to distinguish between different stages of diabetic eye disease, suggesting they could potentially be used as non-invasive biomarkers to help identify or monitor the condition.
This research matters because diabetic retinopathy is a leading cause of vision loss worldwide, and early detection is critical to preventing blindness. Currently, diagnosis requires specialized eye examinations. If validated in larger studies, blood-based biomarkers like SFN and HRNR could offer a more accessible way to screen for or monitor the progression of diabetic eye disease, particularly in patients who may also be developing kidney complications. The authors emphasize that larger studies are needed before these findings can be applied clinically.
Sharmila R, Angayarkanni N, Ratra D, Shanmuganathan S, Lawrence D, Purushothaman K, et al.. (2026). Retinal vasculature-derived proteins serve as potential systemic biomarkers for diabetic retinopathy.. BMJ open ophthalmology. https://doi.org/10.1136/bmjophth-2025-002684