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

Enge, Maria; Bjarnegård, Mattias; Gerhardt, Holger; Gustafsson, Erika LU ; Kalén, Mattias; Asker, Noomi; Hammes, Hans-Peter; Shani, Moshe; Fässler, Reinhardt and Betsholtz, Christer (2002) In EMBO Journal 21(16). p.4307-4316
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
EMBO Journal
volume
21
issue
16
pages
4307 - 4316
publisher
Oxford University Press
external identifiers
  • pmid:12169633
  • wos:000177355300011
  • scopus:18544366585
ISSN
1460-2075
DOI
10.1093/emboj/cdf418
language
English
LU publication?
yes
id
052695b2-447c-49b8-b806-fa1e76f4e5af (old id 109822)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12169633&dopt=Abstract
date added to LUP
2007-07-19 14:48:49
date last changed
2017-12-17 03:56:49
@article{052695b2-447c-49b8-b806-fa1e76f4e5af,
  abstract     = {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 &lt;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.},
  author       = {Enge, Maria and Bjarnegård, Mattias and Gerhardt, Holger and Gustafsson, Erika and Kalén, Mattias and Asker, Noomi and Hammes, Hans-Peter and Shani, Moshe and Fässler, Reinhardt and Betsholtz, Christer},
  issn         = {1460-2075},
  language     = {eng},
  number       = {16},
  pages        = {4307--4316},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy.},
  url          = {http://dx.doi.org/10.1093/emboj/cdf418},
  volume       = {21},
  year         = {2002},
}