TGF-ß2 secretion from RPE decreases with polarization and becomes apically oriented.

ABSTRACT

Retinal pigmented epithelium (RPE) secretes transforming growth factor beta 1 and 2 (TGF-ß1 and -ß2) 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-ß from polarized human RPE (hRPE) and human stem cell derived RPE (hESC-RPE) as compared to nonpolarized cells. TGF-ß2 was the predominant isoform in all cell culture conditions. Nonpolarized cells secreted significantly more TGF-ß2 supporting the contention that loss of polarity of RPE in PVR leads to rise of intravitreal TGF-ß2. Active TGF-ß2, secreted mainly from apical side of polarized RPE, represented 6-10% of total TGF-ß2. In conclusion, polarity is an important determinant of TGF-ß2 secretion in RPE. Low levels of apically secreted active TGF-ß2 may play a role in the normal physiology of the subretinal space. Comparable secretion of TGF-ß from polarized hESC-RPE and hRPE supports the potential for hESC-RPE in RPE replacement therapies.