Photoreceptor-specific overexpression of platelet-derived growth factor induces proliferation of endothelial cells, pericytes, and glial cells and aberrant vascular development: an ultrastructural and immunocytochemical study.
Platelet-derived growth factor (PDGF) is necessary for the normal development of the retinal vasculature and its overexpression is likely to contribute to proliferative retinal disorders, such as proliferative vitreoretinopathy. Transgenic mice that overexpress PDGF-B in the photoreceptors (rho/PDGF-B mice) develop traction retinal detachment. In the present study, a detailed histopathological analysis was performed in rho/PDGF-B mice. In these transgenic mice, endothelial cells, pericytes, and glial cells begin to proliferate at postnatal day 7 (P7). All three cell types increase in numbers, forming a highly vascularized cell mass, which reaches a maximum thickness at P14. Cords of endothelial cells and glia invade the retina and exert traction, generating retinal folds; however, the deep capillary bed never forms. Griffonia simplicifolia isolectin B4 (GSA)-positive endothelial cells form tubes and penetrate the retina to the level of the outer plexiform layer, but they never interconnect to form the deep capillary bed. The vessels within the cell mass are patent, but have a very immature morphology. They often are thin-walled with fenestrations. Pericytes and glial cells are usually found in clusters and are not associated with the abnormal vessels. The lack of this association may account for the failure to form a mature vasculature.
Vinores
Stanley A
SA
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-9289, USA. svinores@jhmi.edu
Seo
Man Seong
MS
Derevjanik
Nancy L
NL
Campochiaro
Peter A
PA
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D010786:Photoreceptor Cells / Q000378:metabolism*; D037121:Plant Lectins / Q000493:pharmacokinetics; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology*; D012163:Retinal Detachment / Q000209:etiology*
D000199:Actins; D005904:Glial Fibrillary Acidic Protein; C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis