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Updated: Aug 29, 2026
An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
Published on: January 25, 2019
Oncofetal fibronectin in diabetic retinopathy
Zia A Khan1, Mark Cukiernik, John R Gonder
1Department of Pathology, University of Western Ontario, London, Ontario, Canada.
Purpose:
Imbalance between extracellular matrix protein synthesis and degradation is a key feature of diabetic retinopathy. Fibronectin, a predominant constituent of the extracellular matrix, has been shown to undergo alternative splicing to produce embryonic isoforms in various pathologic conditions, such as fibrotic diseases and tumorigenesis. Two such isoforms, oncofetal fibronectin variants that are characterized by the inclusion of the oncofetal domains A and B, were the focus of the present study.
Methods:
The expression of oncofetal fibronectin variants was determined in human vitreous samples obtained from patients undergoing vitrectomy for proliferative diabetic retinopathy and nondiabetes-associated ocular conditions such as macular hole. In addition, an animal model of chronic diabetes and cultured endothelial cells was used to elucidate the mechanistic basis for this aberrant expression of oncofetal fibronectin.
Results:
Expression of fibronectin containing the oncofetal domain B was upregulated in the vitreous of patients with diabetic retinopathy.
Conclusions:
Use of a well-established animal model of chronic diabetic complications and cultured endothelial cells showed that diabetes-induced upregulation of oncofetal fibronectin is, in part, dependent on hyperglycemia-induced transforming growth factor-beta1 and endothelin-1. Furthermore, the data suggest that oncofetal fibronectin is involved in endothelial cell proliferation.
Insights
Diabetic retinopathy involves altered extracellular matrix. This study found oncofetal fibronectin variants, specifically domain B, are upregulated in patients with diabetic retinopathy, linked to hyperglycemia and endothelial cell proliferation.
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- Diabetic retinopathy (DR) is characterized by an imbalance in extracellular matrix (ECM) synthesis and degradation.
- Alternative splicing of fibronectin produces embryonic isoforms in pathological conditions like fibrosis and cancer.
- Oncofetal fibronectin variants, including domains A and B, are implicated in disease processes.
Purpose of the Study:
- To investigate the expression of oncofetal fibronectin variants in diabetic retinopathy.
- To elucidate the mechanistic basis for aberrant oncofetal fibronectin expression in diabetes.
Main Methods:
- Analysis of human vitreous samples from patients with proliferative diabetic retinopathy and controls.
- Utilizing a chronic diabetes animal model.
- Employing cultured endothelial cells to study molecular mechanisms.
Main Results:
- Expression of fibronectin containing the oncofetal domain B was significantly upregulated in the vitreous of patients with diabetic retinopathy.
Conclusions:
- Diabetes-induced upregulation of oncofetal fibronectin is partly mediated by hyperglycemia-induced transforming growth factor-beta1 and endothelin-1.
- Oncofetal fibronectin appears to play a role in endothelial cell proliferation in the context of diabetes.
