title: Platelet-derived growth factor over-expression in retinal progenitors results in abnormal retinal vessel formation.
abstract: Platelet-derived growth factor (PDGF) plays an important role in development of the central nervous system, including the retina. Excessive PDGF signaling is associated with proliferative retinal disorders. We reported previously that transgenic mice in which PDGF-B was over-expressed under control of the nestin enhancer, nes/tk-PdgfB-lacZ, exhibited enhanced apoptosis in the developing corpus striatum. These animals display enlarged lateral ventricles after birth as well as behavioral aberrations as adults. Here, we report that in contrast to the relatively mild central nervous system phenotype, development of the retina is severely disturbed in nes/tk-PdgfB-lacZ mice. In transgenic retinas all nuclear layers were disorganized and photoreceptor segments failed to develop properly. Since astrocyte precursor cells did not populate the retina, retinal vascular progenitors could not form a network of vessels. With time, randomly distributed vessels resembling capillaries formed, but there were no large trunk vessels and the intraocular pressure was reduced. In addition, we observed a delayed regression of the hyaloid vasculature. The prolonged presence of this structure may contribute to the other abnormalities observed in the retina, including the defective lamination.
authors.affiliation: Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Per-Henrik D
authors.initials: PH
authors.lastname: Edqvist
authors.forename: Mia
authors.initials: M
authors.lastname: Niklasson
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.forename: Finn
authors.initials: F
authors.lastname: Hallböök
authors.forename: Karin
authors.initials: K
authors.lastname: Forsberg-Nilsson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001549:Benzamides; D015415:Biomarkers / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D007429:Intraocular Pressure / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D012160:Retina / Q000254:growth & development / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012171:Retinal Vessels / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D019076:Transgenes / Q000235:genetics
chemical_list: D001549:Benzamides; D015415:Biomarkers; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D000068877:Imatinib Mesylate