Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives

@article{Caldwell2003VascularEG,
  title={Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives},
  author={Ruth B. Caldwell and Manuela Bartoli and Mohamed Ali Behzadian and Azza B. El-Remessy and Mohamed Al-Shabrawey and Daniel H. Platt and R. William Caldwell},
  journal={Diabetes/Metabolism Research and Reviews},
  year={2003},
  volume={19}
}
Retinal neovascularization and macular edema are central features of diabetic retinopathy, the major cause of blindness in the developed world. Current treatments are limited in their efficacy and are associated with significant adverse effects. Characterization of the molecular and cellular processes involved in vascular growth and permeability has led to the recognition that the angiogenic growth factor and vascular permeability factor vascular endothelial growth factor (VEGF) plays a pivotal… 

Vascular endothelial growth factor and diabetic complications

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...

References

SHOWING 1-10 OF 202 REFERENCES

Advanced glycation end products increase retinal vascular endothelial growth factor expression.

TLDR
It is found that AGEs increased VEGF mRNA levels in the ganglion, inner nuclear, and retinal pigment epithelial (RPE) cell layers of the rat retina, and AGE-induced increases in V EGF expression were dose- and time-dependent, inhibited by antioxidants, and additive with hypoxia.

Vascular endothelial growth factor and its receptors in control and diabetic rat eyes.

TLDR
The changes in retinal expression of VEGF and VEGFR-2 in association with diabetes suggest a role for this pathway in diabetic retinopathy.

Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization.

Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins.

  • L. AielloE. Pierce L. Smith
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
TLDR
VEGF's causal role in retinal angiogenesis is demonstrated and the potential of VEGF inhibition as a specific therapy for ischemic retinal disease is proved.

Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox.

TLDR
Two apparently diametrically opposed therapeutic paradigms are arising for the treatment of vascular complications in diabetes, and as these divergent therapeutic modalities begin to enter the clinical arena, careful consideration of the potential risks, benefits, and interactions of the opposing regimens is required.

Molecular and biological properties of vascular endothelial growth factor

  • N. Ferrara
  • Biology
    Journal of Molecular Medicine
  • 1999
TLDR
Current evidence indicates that VEGF is essential for embryonic vasculogenesis and angiogenesis, and both therapeuticAngiogenesis using recombinant V EGF or VEGFs gene transfer and inhibition of VEGf-mediated pathological angiogenic are being pursued.

Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat.

TLDR
Data obtained from a rodent model in which retinal neovascularization does not occur support the concept that the VEGF/VEGF receptor system is upregulated in early diabetic retinopathy.

Suppression of diabetic retinopathy with angiopoietin-1.

Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.

TLDR
The data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.
...