Retinal pigmented epithelium (RPE) secretes transforming growth factor beta 1 and 2 (TGF-β1 and -β2) cytokines involved in fibrosis, immune privilege, and proliferative vitreoretinopathy (PVR). Since RPE cell polarity may be altered in various disease conditions including PVR and age-related macular degeneration, we determined levels of TGF-β from polarized human RPE (hRPE) and human stem cell derived RPE (hESC-RPE) as compared to nonpolarized cells. TGF-β2 was the predominant isoform in all cell culture conditions. Nonpolarized cells secreted significantly more TGF-β2 supporting the contention that loss of polarity of RPE in PVR leads to rise of intravitreal TGF-β2. Active TGF-β2, secreted mainly from apical side of polarized RPE, represented 6-10% of total TGF-β2. In conclusion, polarity is an important determinant of TGF-β2 secretion in RPE. Low levels of apically secreted active TGF-β2 may play a role in the normal physiology of the subretinal space. Comparable secretion of TGF-β from polarized hESC-RPE and hRPE supports the potential for hESC-RPE in RPE replacement therapies.
Keywords: Embryonic stem cell; Polarity; Proliferative vitreoretinopathy; Retinal pigment epithelium; TGF-β.
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