Attainment of polarity promotes growth factor secretion by retinal pig-ment epithelial cells: Relevance to age-related macular degeneration

Abstract

The antiangiogenic and neurotrophic growth factor, pigment epithelial derived factor (PEDF), and theproangiogenic growth factor, vascular endothelial growth factor-A (VEGF), are released from retinal pigment epithelial(RPE) cells where they play a critical role in the pathogenesis of age-related macular degeneration (AMD). Since RPEpolarity may be altered in advanced AMD, we studied the effect of polarization of differentiated, human RPE monolayercultures on expression and secretion of PEDF and VEGF. Polarized RPE demonstrated apical microvilli, expression of tightjunction proteins, apical localization of Na/K- ATPase, and high transepithelial resistance (490 ± 17 Ω•cm2). PEDF secretionwas about 1000 fold greater than that for VEGF in both polarized and non-polarized cultures. Polarization of the RPEmonolayer increased PEDF secretion, which was predominantly apical, by 34 fold (p<0.02) and VEGF secretion, which waspredominantly basolateral, by 5.7 fold (p<0.02). Treatment of non-polarized RPE cultures with bone morphogeneticprotein-4 (BMP-4) had no effect on PEDF or VEGF secretion, but resulted in a dose-dependent >2-fold increase inbasolateral VEGF secretion (p<0.05) in polarized cultures. Our data show that polarity is an important determinant of thelevel of PEDF and VEGF secretion in RPE and support the contention that loss of polarity of RPE in AMD results in markedloss of neurotrophic and vascular support for the retina potentially leading to photoreceptor loss and blindness. © Sonoda et al.