Platelet-derived Growth Factor Over-Expression in Retinal Progenitors Results in Abnormal Retinal Vessel Formation

PLoS One. 2012;7(8):e42488. doi: 10.1371/journal.pone.0042488. Epub 2012 Aug 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Benzamides
  • Biomarkers / metabolism
  • Capillaries / drug effects
  • Capillaries / growth & development
  • Capillaries / metabolism
  • Capillaries / pathology
  • Cell Death / drug effects
  • Cell Lineage / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression / drug effects
  • Humans
  • Imatinib Mesylate
  • Intraocular Pressure / drug effects
  • Mice
  • Mice, Transgenic
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-sis / metabolism*
  • Pyrimidines / pharmacology
  • Retina / growth & development
  • Retina / metabolism
  • Retina / pathology*
  • Retina / physiopathology
  • Retinal Vessels / growth & development*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology*
  • Retinal Vessels / physiopathology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Time Factors
  • Transgenes / genetics

Substances

  • Benzamides
  • Biomarkers
  • Piperazines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-sis
  • Pyrimidines
  • Imatinib Mesylate

Grant support

This study was supported by grants to KFN from the Swedish Cancer Society (www.cancerfonden.se Grant 070079), Swedish Research Council (www.vr.se 319-2008-2557) and Swedish Childhood Cancer Foundation (www.barncancerfonden.se PROJ07/017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.