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Updated: Jun 26, 2026
An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
Published on: January 25, 2019
Fibrocontractive Müller cell phenotypes in proliferative diabetic retinopathy
Clyde Guidry1, Jeffery L King, John O Mason
1Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama 352994, USA. cguidry@uab.edu
Purpose:
To evaluate Müller cells as a potential source of fibrocontractive cells in proliferative diabetic retinopathy.
Methods:
Temporal changes in glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, and alpha smooth muscle actin (alphaSMA) expression in cultures of freshly isolated porcine Müller cells were evaluated by indirect immunofluorescence and Western blotting. A similar evaluation was performed on freshly isolated Müller cells maintained in high- and low-glucose culture. Cryosections of six diabetic epiretinal tissues were evaluated for the same antigens.
Results:
Müller cell changes in culture included loss of glutamine synthetase and GFAP, with coincident gains in alphaSMA immunoreactivity. Vimentin immunoreactivity persisted without obvious change. Similar changes were observed when the cells were maintained in high- or low-glucose culture medium. All six diabetic epiretinal membranes contained positively identified Müller cells with vimentin, GFAP, and glutamine synthetase immunoreactivities. There was a progressive loss of glutamine synthetase and GFAP content and a coincident increase in alphaSMA content as the cells assumed an elongated, fibroblastlike morphology.
Conclusions:
Continuous culture in high- versus low-glucose medium does not influence Müller cell phenotype changes. Positively identified Müller cells are present in diabetic epiretinal tissues and appear to undergo the same progression of phenotype changes observed in culture. Cells capable of generating tractional forces associated with proliferative diabetic retinopathy can arise from Müller cells.
Insights
Müller cells in the eye can transform into fibrocontractive cells, contributing to proliferative diabetic retinopathy. This transformation occurs independently of glucose levels, suggesting Müller cells are a key source of these disease-driving cells.
Area of Science:
- Ophthalmology
- Cell Biology
- Diabetic Retinopathy Research
Background:
- Proliferative diabetic retinopathy (PDR) is a leading cause of vision loss.
- Fibrocontractive membranes in PDR exert tractional forces, leading to retinal detachment.
- The cellular origin of these fibrocontractive cells remains incompletely understood.
Purpose of the Study:
- To investigate Müller cells as a potential source of fibrocontractive cells in PDR.
- To characterize phenotypic changes in Müller cells associated with fibrocontraction.
Main Methods:
- Porcine Müller cells were cultured and analyzed for glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase, and alpha smooth muscle actin (alphaSMA) expression.
- Immunofluorescence and Western blotting were used to assess protein expression.
- Diabetic epiretinal tissues were examined for Müller cell markers.
Main Results:
- Müller cells in culture exhibited a loss of glutamine synthetase and GFAP, with increased alphaSMA expression, adopting a fibroblast-like morphology.
- These phenotypic changes occurred regardless of high- or low-glucose culture conditions.
- Diabetic epiretinal membranes contained Müller cells showing similar changes, including increased alphaSMA and loss of specific markers, correlating with a fibrocontractive phenotype.
Conclusions:
- Müller cells present in diabetic epiretinal tissues undergo phenotypic changes similar to those observed in culture.
- These changes indicate that Müller cells can transform into cells capable of generating tractional forces.
- Müller cells are identified as a significant source of fibrocontractive cells in proliferative diabetic retinopathy.
