SDF-1 is both necessary and sufficient to promote proliferative retinopathy. Academic Article uri icon

Overview

MeSH

  • Adrenal Cortex Hormones
  • Adult
  • Animals
  • Antibodies
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CXCL12
  • Humans
  • Ischemia
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Retinal Neovascularization
  • Titrimetry
  • Triamcinolone

MeSH Major

  • Chemokines, CXC
  • Diabetic Retinopathy

abstract

  • Diabetic retinopathy is the leading cause of blindness in working-age adults. It is caused by oxygen starvation in the retina inducing aberrant formation of blood vessels that destroy retinal architecture. In humans, vitreal stromal cell-derived factor-1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses. Treatment of patients with triamcinolone decreases SDF-1 levels in the vitreous, with marked disease improvement. SDF-1 induces human retinal endothelial cells to increase expression of VCAM-1, a receptor for very late antigen-4 found on many hematopoietic progenitors, and reduce tight cellular junctions by reducing occludin expression. Both changes would serve to recruit hematopoietic and endothelial progenitor cells along an SDF-1 gradient. We have shown, using a murine model of proliferative adult retinopathy, that the majority of new vessels formed in response to oxygen starvation originate from hematopoietic stem cell-derived endothelial progenitor cells. We now show that the levels of SDF-1 found in patients with proliferative retinopathy induce retinopathy in our murine model. Intravitreal injection of blocking antibodies to SDF-1 prevented retinal neovascularization in our murine model, even in the presence of exogenous VEGF. Together, these data demonstrate that SDF-1 plays a major role in proliferative retinopathy and may be an ideal target for the prevention of proliferative retinopathy.

publication date

  • January 2005

has subject area

  • Adrenal Cortex Hormones
  • Adult
  • Animals
  • Antibodies
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC
  • Diabetic Retinopathy
  • Humans
  • Ischemia
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Retinal Neovascularization
  • Titrimetry
  • Triamcinolone

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC539202

Digital Object Identifier (DOI)

  • 10.1172/JCI22869

PubMed ID

  • 15630447

Additional Document Info

start page

  • 86

end page

  • 93

volume

  • 115

number

  • 1