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
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:https://doi.org/
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    • Get Citation

      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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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