Novel mechanism for age-related macular degeneration: An equilibrium shift between the angiogenesis factors VEGF and PEDF

Kyoko Ohno-Matsui, Ikuo Morita, Joyce Tombran-Tink, David Mrazek, Mitsue Onodera, Tomoko Uetama, Masato Hayano, Sei Itsu Murota, Manabu Mochizuki

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Abstract

We investigated gene expression profiles of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in differentiated and non-differentiated retinal pigment epithelial (RPE) cells during oxidative stress. Human RPE cells were grown in culture on laminin-coated flasks to obtain differentiated features. Cells cultured on plastic were used as non-differentiated controls. After confluence, hydrogen peroxide (H2O2) was added for 48 h, then, total RNA was extracted and used for RT-PCR and Northern blot analysis. Medium conditioned by RPE was used for ELISA, Western blotting, and in vitro angiogenesis assay. As a result, differentiated RPE cells expressed significantly higher levels of VEGF protein, as compared to their non-differentiated counterparts. The expression pattern remained consistent even after cellular exposure to H2O2. Conversely, while elevated levels of PEDF transcript and protein were seen in differentiated RPE cells, compared to non-differentiated cells, a marked decrease at both PEDF mRNA and protein levels was seen after treatment with H2O2. Moreover, this decrease in PEDF expression was dosage dependent. In in vitro angiogenesis assay, conditioned medium from differentiated human RPE cells after exposure to H2O2 showed a dramatic increase in tubular formation and migratory activity of microvascular endothelial cells. These data suggest that, in physiological conditions, a critical balance between PEDF and VEGF exists, and PEDF may counteract the angiogenic potential of VEGF. Under oxidative stress, PEDF decreases disrupting this balance. This equilibrium shift may be significant in promoting a pathological condition of RPE cells and contributing to choroidal neovascularization in age-related macular degeneration.

Original languageEnglish (US)
Pages (from-to)323-333
Number of pages11
JournalJournal of Cellular Physiology
Volume189
Issue number3
DOIs
StatePublished - Nov 26 2001

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Ohno-Matsui, K., Morita, I., Tombran-Tink, J., Mrazek, D., Onodera, M., Uetama, T., Hayano, M., Murota, S. I., & Mochizuki, M. (2001). Novel mechanism for age-related macular degeneration: An equilibrium shift between the angiogenesis factors VEGF and PEDF. Journal of Cellular Physiology, 189(3), 323-333. https://doi.org/10.1002/jcp.10026