Abstract
We previously demonstrated that differentiated retinal pigment epithelial (RPE) cells express high levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), and a critical balance between VEGF and PEDF is important to prevent the development of choroidal neovascularization. We report here that VEGF secreted by RPE cells upregulates PEDF expression via VEGFR-1 in an autocrine manner. PEDF mRNA and protein expression was downregulated by neutralizing antibody against VEGF in differentiated human RPE cells. VEGFR-1 neutralization decreased PEDF mRNA and protein expression whereas anti-VEGFR-2 antibody had no effect. Addition of placenta growth factor (PlGF) restored PEDF expression in the presence of anti-VEGF antibody. These results demonstrate a regulatory interaction between angiogenesis stimulators and inhibitors to maintain homeostasis in normal human retina.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cells, Cultured
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Endothelial Growth Factors / antagonists & inhibitors
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Endothelial Growth Factors / physiology*
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Eye Proteins*
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Feedback
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Gene Expression / drug effects
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Humans
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Intercellular Signaling Peptides and Proteins / physiology*
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Lymphokines / antagonists & inhibitors
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Lymphokines / physiology*
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Neovascularization, Physiologic
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Nerve Growth Factors*
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Pigment Epithelium of Eye / blood supply
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Pigment Epithelium of Eye / cytology
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Pigment Epithelium of Eye / drug effects
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Pigment Epithelium of Eye / physiology*
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Placenta Growth Factor
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Pregnancy Proteins / pharmacology
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Protein Biosynthesis
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Proteins / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Serpins / biosynthesis
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Serpins / genetics*
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Up-Regulation
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-1 / genetics*
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Vascular Endothelial Growth Factor Receptor-1 / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-2 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
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Vascular Endothelial Growth Factors
Substances
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Endothelial Growth Factors
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Eye Proteins
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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Nerve Growth Factors
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PGF protein, human
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Pregnancy Proteins
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Proteins
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RNA, Messenger
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Serpins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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pigment epithelium-derived factor
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Placenta Growth Factor
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2