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Published on: January 25, 2019
Expression of myofibroblast activation molecules in proliferative vitreoretinopathy epiretinal membranes
Ahmed M Abu El-Asrar1, Luc Missotten, Karel Geboes
1Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
Purpose:
Fibrotic disorders are associated with activation of fibroblasts into extracellular matrix-secreting myofibroblasts expressing α-smooth muscle actin (α-SMA). Myofibroblasts are the predominant cellular component of proliferative vitreoretinopathy (PVR) epiretinal membranes. We investigated the expression of molecules involved in myofibroblast activation, migration and proliferation in PVR epiretinal membranes.
Methods:
Fifteen membranes were studied by immunohistochemical techniques using monoclonal and polyclonal antibodies directed against snail, fibroblast activation protein (FAP), CD44, hydrogen peroxide-inducible clone-5 (Hic-5), galectin-3, interleukin-13 receptor α2 (IL-13Rα2) and receptor for advanced glycation end products (RAGE).
Results:
Myofibroblasts expressing α-SMA were present in all membranes. Myofibroblasts expressed nuclear immunoreactivity for Snail and Hic-5, cytoplasmic immunoreactivity for FAP, IL-13Rα2 and RAGE and membranous immunoreactivity for CD44. There was no immunoreactivity for galectin-3. The number of cells expressing α-SMA correlated significantly with the number of cells expressing Snail (r = 0.56; p = 0.03), Hic-5 (r = 0.526; p = 0.044), IL-13Rα2 (r = 0.773; p = 0.001) and RAGE (r = 0.734; p = 0.002).
Conclusions:
Snail, FAP, CD44, Hic-5, IL13Rα2 and RAGE may be involved in proliferative events occurring in PVR.
Insights
Fibrotic disorders involve myofibroblast activation. This study found Snail, Hic-5, IL-13Rα2, and RAGE are significantly correlated with α-SMA in proliferative vitreoretinopathy membranes, suggesting their role in disease progression.
Area of Science:
- Ophthalmology
- Cell Biology
- Fibrosis Research
Background:
- Fibrotic disorders are characterized by myofibroblast activation.
- Myofibroblasts expressing α-smooth muscle actin (α-SMA) are key in proliferative vitreoretinopathy (PVR).
- Understanding molecular drivers of myofibroblast activation in PVR is crucial.
Purpose of the Study:
- To investigate the expression of key molecules in PVR epiretinal membranes.
- To identify proteins involved in myofibroblast activation, migration, and proliferation in PVR.
Main Methods:
- Immunohistochemical analysis of 15 PVR epiretinal membranes.
- Antibodies used targeted Snail, fibroblast activation protein (FAP), CD44, Hic-5, galectin-3, IL-13Rα2, and RAGE.
- Quantification of α-SMA positive cells and correlation with other markers.
Main Results:
- All membranes contained α-SMA positive myofibroblasts.
- Snail, Hic-5, FAP, IL-13Rα2, and RAGE were expressed in myofibroblasts.
- Significant correlations were found between α-SMA and Snail, Hic-5, IL-13Rα2, and RAGE expression.
Conclusions:
- Snail, FAP, CD44, Hic-5, IL-13Rα2, and RAGE are implicated in the proliferative processes of PVR.
- These molecules represent potential therapeutic targets for PVR treatment.
- Further research is warranted to elucidate their precise roles in PVR pathogenesis.
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