Photoreceptor-specific expression of platelet-derived growth factor-B results in traction retinal detachment.
Expression of platelet-derived growth factor (PDGF)-A and PDGF-B is increased in patients with proliferative retinopathies in which traction retinal detachments occur. Previous studies have demonstrated that increased expression of PDGF-A in the retina of transgenic mice results in retinal gliosis due to proliferation of astrocytes with different retinal phenotypes based on the time of onset and location of the PDGF-A production. In this study, we investigated the effects of PDGF-B in the retina using gain-of-function transgenic mice that express PDGF-B in photoreceptors. These mice show proliferation of astrocytes, pericytes, and, to a lesser extent, endothelial cells, resulting in ectopic cells on the surface and extending into the retina. The sheets of cells exert traction on the retina resulting in traction retinal detachments similar to those seen in humans with proliferative retinopathies. These studies suggest that PDGF-B has more dramatic effects in the retina than PDGF-A, because it acts on additional cell types, in particular on pericytes, which have a highly developed contractile apparatus. These studies in the retina suggest a means that could be used in other tissues throughout the body to achieve graded PDGF effects. They also provide a new model of traction retinal detachment that can be used to investigate new treatments for patients with proliferative retinopathies.
Seo
M S
MS
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Okamoto
N
N
Vinores
M A
MA
Vinores
S A
SA
Hackett
S F
SF
Yamada
H
H
Yamada
E
E
Derevjanik
N L
NL
LaRochelle
W
W
Zack
D J
DJ
Campochiaro
P A
PA
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012163:Retinal Detachment / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005904:Glial Fibrillary Acidic Protein; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A