Platelet-derived growth factor-A-induced retinal gliosis protects against ischemic retinopathy.
Retinal astrocytes are located in the nerve fiber layer and along retinal blood vessels and have been hypothesized to participate in the induction and maintenance of the blood-retinal barrier. Platelet-derived growth factor-A (PDGF-A) is normally produced by retinal ganglion cells and is involved in astrocyte recruitment and proliferation. We used gain-of-function transgenic mice that express PDGF-A in photoreceptors to explore the roles of PDGF-A and astrocytes in the retina. Transgene-positive mice developed glial infiltration of the inner retina and had significantly less oxygen-induced retinal vascular closure and no neovascularization compared with littermate controls, which had prominent vascular closure and neovascularization. The increased survival of endothelial cells in transgenic mice in the face of oxygen-induced down-regulation of vascular endothelial growth factor was accompanied by an increase in astrocyte-derived fibroblast growth factor-2. Therefore, PDGF-A increases retinal astrocytes, which promote the survival of endothelial cells as well as their expression of barrier characteristics.
Yamada
H
H
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Yamada
E
E
Ando
A
A
Seo
M S
MS
Esumi
N
N
Okamoto
N
N
Vinores
M
M
LaRochelle
W
W
Zack
D J
DJ
Campochiaro
P A
PA
D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced*; D018496:Hyperoxia / Q000139:chemically induced / Q000503:physiopathology; D007511:Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010100:Oxygen; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects* / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D012243:Rhodopsin; D010100:Oxygen