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

  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},
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

Antivascular endothelial growth factor in diabetic retinopathy.

A high level of V EGF has been detected in eyes presenting DME and PDR, and thereby VEGF is an attractive candidate as therapeutic target of pharmacological treatment in the management of DR.

Diabetic Retinopathy and Inflammation: Novel Therapeutic Targets

It is possible that the novel selective inhibitors of the inflammatory cascade (like angiopoietin-2, TNFα, and chemokines) may be useful therapeutic agents in the treatment of diabetic macular edema (DME), either alone or in combination with the anti-VEGF drugs.

Rat strain-dependent susceptibility to ischemia-induced retinopathy associated with retinal vascular endothelial growth factor regulation.

A single nucleotide polymorphism (SNP) at upstream stimulating factor-binding site in the VEGF promoter region between BN and SD rats was identified and found to be associated with a high susceptibility to retinal vascular leakage in BN rats.

Oxidative stress modulates the expression of VEGF isoforms in the diabetic retina

The retina of the Ins2Akita diabetic mice was shown to have decreased levels of the anti-angiogenic VEGF165b protein and a high production of reactive oxygen species (ROS).

Vascular endothelial growth factor and the potential therapeutic use of pegaptanib (macugen) in diabetic retinopathy.

Pegaptanib, a novel RNA aptamer currently used in the treatment of agerelated macular degeneration, binds and inactivates VEGF165 and has been shown in animal models to reverse the blood-retinal barrier breakdown associated with diabetes.

Long-term global retinal microvascular changes in a transgenic vascular endothelial growth factor mouse model

Analysis of diabetic retinopathy-like changes revealed that these parameters were tightly correlated with the initial degree of vascular leakage; low levels reflected slow and limited retinal microvascular changes in mild cases and high levels reflected more rapid and extensive changes in moderate cases.

Role of cytokines and trophic factors in the pathogenesis of diabetic retinopathy.

Recent research regarding the clinical and laboratory findings of diabetic retinopathy is summarized to uncover the detailed pathogenesis of DR, which may lead to new therapeutic strategies.

[In vitro studies on the mechanism of action of VEGF and its inhibitors].

The influence of V EGF isoforms and the inhibitor ranibizumab on the proliferation and migration of bovine retinal microvascular endothelial cells was studied, as well as the rearrangement of tight-junction proteins after treatment of the cells with VEGF(165) and specific inhibitors.



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

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.

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
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.

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
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.

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.

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.