May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Selective Increase in Basolateral Secretion of VEGF Upon BMP-4 Treatment of Highly Polarized Human RPE Cells
S. Sonoda; P. G. Sreekumar; C. Spee; S. J. Ryan; R. Kannan; D. R. Hinton
Author Affiliations & Notes
  • S. Sonoda
    Arnold and Mabel Beckman Macular Research center, Doheny Eye Institute, Los Angeles, California
    Departments of Ophthalmology,
    Keck School of Medicine of the University of Southern California, Los Angeles, California
  • P. G. Sreekumar
    Arnold and Mabel Beckman Macular Research center, Doheny Eye Institute, Los Angeles, California
    Departments of Ophthalmology,
    Keck School of Medicine of the University of Southern California, Los Angeles, California
  • C. Spee
    Arnold and Mabel Beckman Macular Research center, Doheny Eye Institute, Los Angeles, California
    Departments of Ophthalmology,
    Keck School of Medicine of the University of Southern California, Los Angeles, California
  • S. J. Ryan
    Arnold and Mabel Beckman Macular Research center, Doheny Eye Institute, Los Angeles, California
    Departments of Ophthalmology,
    Keck School of Medicine of the University of Southern California, Los Angeles, California
  • R. Kannan
    Arnold and Mabel Beckman Macular Research center, Doheny Eye Institute, Los Angeles, California
    Departments of Ophthalmology,
    Keck School of Medicine of the University of Southern California, Los Angeles, California
  • D. R. Hinton
    Arnold and Mabel Beckman Macular Research center, Doheny Eye Institute, Los Angeles, California
    Departments of Pathology,
    Keck School of Medicine of the University of Southern California, Los Angeles, California
  • Footnotes
    Commercial Relationships  S. Sonoda, None; P.G. Sreekumar, None; C. Spee, None; S.J. Ryan, None; R. Kannan, None; D.R. Hinton, None.
  • Footnotes
    Support  NIH Grants EY03040, EY01545, Arnold and Mabel Beckman Foundation and RPB.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 855. doi:
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      S. Sonoda, P. G. Sreekumar, C. Spee, S. J. Ryan, R. Kannan, D. R. Hinton; Selective Increase in Basolateral Secretion of VEGF Upon BMP-4 Treatment of Highly Polarized Human RPE Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):855.

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Abstract

Purpose: : Bone morphogenetic protein-4 (BMP-4) is a member of the TGF-beta superfamily and plays an important role in development, morphogenesis, cell proliferation and apoptosis. It is expressed in a number of tissues including the retina. We investigated the effect of exogenous BMP-4 on secretion of two key angiogenic growth factors, VEGF and PEDF, by the apical and basolateral domains of highly polarized human RPE.

Methods: : Highly differentiated RPE cells were grown on Transwell filters (12 mm, 0.4µm pore size). RPE cells were cultured in a differentiation media modified from that previously described by Hu and Bok (Mol Vis. 2001; 7:14-9) for 1 month. The integrity and resistance of the RPE monolayer was evaluated by measuring transepithelial resistance (TER) and staining for tight junction (TJ) proteins. Human recombinant BMP-4 (10, 25, 50, 75 and 100 ng/ml) was introduced to the apical and basolateral transwells in serum-free medium. Cellular expression and secretion of VEGF-A and PEDF to the apical and basolateral domains were determined by ELISA after 24 h.

Results: : The integrity of RPE layer was confirmed by expression of TJ proteins ZO-1 and occludin and apical localization of Na/K-ATPase. The TER averaged 503.2 ± 128.4 ohms.cm2 and did not change after BMP-4 treatment. A dose-dependent increase in basolateral secretion of VEGF was observed after BMP-4 from 830.1± 232.7 pg/ml in untreated control to a maximal level of 3034.7± 78.6 with 100 ng/ml while the apical secretion showed no apparent change. PEDF secretion from both apical and basolateral domains was unaffected by BMP-4 treatment. The VEGF to PEDF ratios were 1.1, 1.7, 2.2, 2.4 and 3.0 with 10, 25, 50 and 75 and 100 ng/ml, respectively (Control ratio = 1). The intracellular VEGF and PEDF levels were not significantly altered by BMP-4 treatment.

Conclusions: : Our data suggest that BMP-4 may play a significant role in the regulation of angiogenesis in RPE by stimulating VEGF secretion to the choroidal side and by augmenting VEGF/PEDF ratios.

Keywords: age-related macular degeneration • growth factors/growth factor receptors • neovascularization 
© 2008, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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