Date of Award
Campus Access Dissertation
Richard C Hunt
Proliferative vitreoretinopathy (PVR) is a fibrotic eye disease and the most common cause of fail ure of retinal reattachment surgery. Although the etiology of this disease is unknown, TGFβ has been implicated as a key factor contributing to PVR.
The risk factors of PVR include a tear on the neural retina, breakdown of blood-retinal barrier, and inflammation. Retinal pigment epithelial (RPE) cells, a single layer of cuboidal epithelium located at the back of eye behind neural retina, gain access and proliferate in the vitreous during PVR. RPE cells in the vitreous undergo epithelial-mesenchymal transformation (EMT) and participate in the formation of contractile epiretinal membrane.
In vitro, human RPE cells in the presence of vitreous undergo a similar transformation as they do in PVR in vivo. In 25% vitreous, RPE cells become fibrotic, migratory and invasive. Besides, EMT-related genes (Snail, Slug, α5integrin and FN-EDA) in RPE cells are elevated by vitreous. TGFβ is indispensable for vitreous-mediated RPE cells transformation in vitro. Vitreous also induces BMP and IL1β expressions. The combination of TBI up-regulates EMT-related genes as vitreous does. TGFβ alone induces a different type of transformation of RPE cells with stress fiber formation. TGFβ induces Snail, α5integrin and FN-EDA expressions, but decreases Slug expression. Furthermore, TGFβ induces myofibroblast markers (αSMA and CTGF), although vitreous suppresses their expressions. Vitreous also down-regulates the expression of TGFβ. The combination of TBI replicates the effect of vitreous as it decreases αSMA and CTGF. IL1β suppresses myofibroblast markers. In a dose- dependent manner, IL1β decreases αSMA and CTGF expressions that are elevated by TGFβ. This suggests that IL1β and its related factors play an important role in counteracting the effect of TGFβ.
Chang, B.(2010). The Transformation of Human Retinal Pigment Epithelial Cells. (Doctoral dissertation). Retrieved from http://scholarcommons.sc.edu/etd/2094