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  • The EMBO Journal (2002) 21, 4307 - 4316
  • doi:10.1093/emboj/cdf418

Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy

Maria Enge1, Mattias Bjarnegård1, Holger Gerhardt1, Erika Gustafsson2, Mattias Kalén3, Noomi Asker3, Hans-Peter Hammes4, Moshe Shani5, Reinhardt Fässler6 and Christer Betsholtz1

  1. Department of Medical Biochemistry, Göteborg University, PO Box 440, SE 405 30 Göteborg, Sweden
  2. Department of Experimental Pathology, Lund University, SE 221 85 Lund, Sweden
  3. AngioGenetics AB, Medicinaregatan 7, SE 413 90 Göteborg, Sweden
  4. Vth Medical Clinic, Medical Faculty of the University of Heidelberg, D-68135 Mannheim, Germany
  5. Institute of Animal Science, The Volcani Center, Bet Dagan 50250, Israel
  6. Max Planck Institute for Biochemistry, Department of Molecular Medicine, Am Klopferspitz 18a, D-82152 Martinsried, Germany

Correspondence to:

Christer Betsholtz, E-mail: Christer.Betsholtz@medkem.gu.se

Received 6 May 2002; Accepted 19 June 2002; Revised 13 June 2002

Loss of pericytes from the capillary wall is a hallmark of diabetic retinopathy, however, the pathogenic significance of this phenomenon is unclear. In previous mouse gene knockout models leading to pericyte deficiency, prenatal lethality has so far precluded analysis of postnatal consequences in the retina. We now report that endothelium-restricted ablation of platelet-derived growth factor-B generates viable mice with extensive inter- and intra-individual variation in the density of pericytes throughout the CNS. We found a strong inverse correlation between pericyte density and the formation of a range of retinal microvascular abnormalities strongly reminiscent of those seen in diabetic humans. Proliferative retinopathy invariably developed when pericyte density was <50% of normal. Our data suggest that a reduction of the pericyte density is sufficient to cause retinopathy in mice, implying that pericyte loss may also be a causal pathogenic event in human diabetic retinopathy.

  • Keywords:

    • Cre-loxP system,
    • diabetes,
    • pericytes,
    • platelet-derived growth factor,
    • retinopathy