Expression of myofibroblast activation molecules in proliferative vitreoretinopathy epiretinal membranes

Purpose: Fibrotic disorders are associated with activation of fibroblasts into extracellular matrix-secreting myofibroblasts expressing alpha-smooth muscle actin (alpha-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 alpha 2 (IL-13R alpha 2) and receptor for advanced glycation end products (RAGE). Results: Myofibroblasts expressing alpha-SMA were present in all membranes. Myofibroblasts expressed nuclear immunoreactivity for Snail and Hic-5, cytoplasmic immunoreactivity for FAP, IL-13R alpha 2 and RAGE and membranous immunoreactivity for CD44. There was no immunoreactivity for galectin-3. The number of cells expressing alpha-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-13R alpha 2 (r = 0.773; p = 0.001) and RAGE (r = 0.734; p = 0.002). Conclusions: Snail, FAP, CD44, Hic-5, IL13R alpha 2 and RAGE may be involved in proliferative events occurring in PVR.