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An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
Published on: January 25, 2019
Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy
Kazunori Tamaki1, Ayumi Usui-Ouchi1, Akira Murakami2
1Department of Ophthalmology, Juntendo University Urayasu Hospital, Chiba, Japan.
Purpose:
The purpose of this study was to investigate whether fibrocytes participate in formation of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR).
Methods:
Vitreous fluid and FVM samples were obtained during vitrectomy in patients with PDR. Samples from patients with macular hole or epiretinal membrane were used as controls. Vitreous fluid and FVM samples were subjected to immunohistochemical analysis. In addition, cells isolated from the vitreous fluid of PDR and control patients were cultured in serum-free medium. Fibrocytes were identified among these cells by morphological and immunohistochemical analyses. We examined the number of fibrocytes in PDR patients and control patients. Also, the concentrations of monocyte chemoattractant protein-1 (MCP-1), pentraxin3, and serum amyloid P (SAP) in vitreous fluid samples from PDR patients and control patients were determined by enzyme-linked immunosorbent assay.
Results:
Fibrocytes were observed in the vitreous and FVM samples from PDR patients. Cells cultured from the vitreous samples of PDR patients were spindle shaped and expressed fibrocyte markers. TGF-β1 induced differentiation of these cells into myofibroblasts. The number of fibrocytes was higher in samples from PDR patients than in samples from control patient. The vitreous fluid concentration of MCP-1 was significantly higher in PDR patients than in controls and showed a significant positive correlation with the number of fibrocytes from the vitreous fluid. Vitreous fluid concentrations of pentraxin3 and SAP were also higher in PDR patients than in control patients.
Conclusions:
These findings indicate that fibrocytes may be involved in development of the FVM in PDR.
Insights
Fibrocytes, a type of immune cell, were found in higher numbers in patients with proliferative diabetic retinopathy (PDR). These cells may play a role in the formation of the fibrovascular membrane (FVM) in PDR.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes mellitus.
- The formation of fibrovascular membranes (FVM) is a hallmark of PDR, leading to vision loss.
- The cellular origins of FVM in PDR remain incompletely understood.
Purpose of the Study:
- To investigate the presence and role of fibrocytes in the development of FVM in patients with PDR.
- To compare the number of fibrocytes in PDR patients with control subjects.
- To analyze the correlation between fibrocytes and specific inflammatory markers in the vitreous fluid of PDR patients.
Main Methods:
- Vitreous fluid and FVM samples were collected from PDR patients and controls during vitrectomy.
- Immunohistochemical analysis was performed on tissue samples.
- Cells isolated from vitreous fluid were cultured and analyzed for fibrocyte markers.
- Enzyme-linked immunosorbent assays (ELISA) were used to quantify MCP-1, pentraxin3, and SAP levels in vitreous fluid.
Main Results:
- Fibrocytes were identified in vitreous and FVM samples from PDR patients.
- The number of fibrocytes was significantly higher in PDR patients compared to controls.
- Vitreous fluid from PDR patients showed elevated levels of MCP-1, pentraxin3, and SAP.
- MCP-1 concentration positively correlated with the number of fibrocytes in the vitreous.
Conclusions:
- Fibrocytes are present in the fibrovascular membranes of PDR patients.
- The increased presence of fibrocytes and associated inflammatory markers suggests their involvement in FVM formation.
- These findings highlight fibrocytes as potential therapeutic targets for PDR.

