PEDF derived from glial Müller cells: a possible regulator of retinal angiogenesis.
A precise balance between stimulators and inhibitors of angiogenesis, such as vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), respectively, is essential for angiogenic homeostasis in ocular tissues. Retinal hypoxia is accompanied by some pathological conditions that may promote intraocular neovascularization. Here we demonstrate that retinal glial (Müller) cells express and release pigment epithelium-derived factor (PEDF). Decreasing oxygen concentrations cause strong attenuation of PEDF release resulting in enhanced VEGF/PEDF ratios. Exposure of Müller cells to VEGF suppressed PEDF release in a dose-dependent manner. This may represent a novel mechanism of ocular angiogenic homeostasis sufficient in the control of PEDF levels during normoxia or mild hypoxia but supplemented by other (hitherto unknown) mechanisms in cases of strong hypoxia. In spite of the enhanced VEGF/PEDF ratios resulting from hypoxia, conditioned media of Müller cells failed to stimulate additional proliferation of retinal endothelial cells. These findings suggest that in the ischemic retina, Müller cells generate a permissive condition for angiogenesis by secreting more VEGF and less PEDF, but the onset of retinal endothelial cell proliferation requires another triggering signal that remains to be identified.
Eye Hospital, University of Leipzig, D-04103 Leipzig, Germany. eichwolf@rz.uni-leipzig.de
Wolfram
W
Eichler
Yousef
Y
Yafai
Thurid
T
Keller
Peter
P
Wiedemann
Andreas
A
Reichenbach
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005136:Eye Proteins; D006168:Guinea Pigs; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D012161:Retinal Artery / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism / Q000503:physiopathology; D015843:Serpins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D000099174:Pigment Epithelium-Derived Factor
D017077:Culture Media, Conditioned; D005136:Eye Proteins; D009414:Nerve Growth Factors; D011506:Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor