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Glial cells as producers of VEGF and opponents in the retina
Author(s) -
EICHLER WOLFR
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.3215.x
Subject(s) - pedf , retina , angiogenesis , vascular endothelial growth factor , microbiology and biotechnology , transforming growth factor , smad , neovascularization , vascular endothelial growth factor a , vascular endothelial growth factor b , biology , transforming growth factor beta , retinal pigment epithelium , cancer research , neuroscience , vegf receptors
Vascular endothelial growth factor (VEGF) is a key cytokine for the development of pathologic neovascularization in the retina. While Müller glial cells upregulate VEGF in the ischemic retina they constitutively secrete anti‐angiogenic factors such as pigment epithelium‐derived factor (PEDF) and transforming growth factor (TGF)‐β2, thereby determining an anti‐proliferative milieu for microvascular endothelial cells. Neutralization of PEDF or TGF‐β partially abrogates the angiostatic action of Müller cells. PEDF and TGF‐β2 are able to control retinal endothelial cell proliferation via suppressing the activity of ERK‐1/‐2 MAP kinases, even in VEGF‐stimulated cells. TGF‐β2 exerts its anti‐proliferative effect through increased Smad phosphorylation. Exposure of retinal endothelial cells to TGF‐β2 or Müller‐cell derived secreted factors causes an increased activation of Smad2/3, which leads to a decreased ERK‐1/‐2 phosphorylation. Given their impact on endothelial signaling and cell growth, Müller cells have emerged as an important cellular element for the control of angiogenesis and retinal neovascularization.