Article

Vascular endothelial growth factor and diabetic complications.

Pfizer, Inc., New York, NY, USA.
Progress in Retinal and Eye Research (impact factor: 9.45). 11/2008; 27(6):608-21. DOI:10.1016/j.preteyeres.2008.09.002
Source: PubMed

ABSTRACT Intraocular delivery of anti-vascular endothelial growth factor (VEGF) therapies is now used widely to treat age-related macular degeneration, and is currently undergoing evaluation in clinical trials for treatment of diabetic retinopathy. An important aspect of anti-VEGF treatment is that while the agents are injected into the vitreous cavity, they may be absorbed systemically, thus potentially affecting systemic VEGF levels. Systemic VEGF-A and the interplay between membrane-bound VEGF receptors and the soluble form of VEGF-R1 are key to angiogenesis, vasculogenesis, neurogenesis and hemodynamics. These cellular processes are regulated by complicated negative and positive feedback loops, many of which are disrupted and altered in diabetes. The VEGF protein, mRNA, as well as the actual VEGF receptor levels, appear to be impaired in diabetes in microvascular and macrovascular vessel beds. What is not clear is the exact role and influence that these levels have on an organ's function. In some organ systems, elevated VEGF levels act as a pathologic angiogenic stimulus (i.e., ocular neovascularization) whereas in others, low levels of VEGF activity leads to pathology (i.e., cardiomyopathy, wound healing and peripheral neuropathy). Diabetic patients have a higher risk of hypertension and proteinuria, two surrogate markers of systemic VEGF inhibition. Certain intraocular anti-VEGF treatments could therefore have an adverse effect in this population by possibly affecting circulating and organ-specific VEGF and VEGF receptor levels.

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Keywords

actual VEGF receptor levels
 
anti-vascular endothelial growth factor
 
cellular processes
 
Certain intraocular anti-VEGF treatments
 
clinical trials
 
Diabetic patients
 
diabetic retinopathy
 
Intraocular delivery
 
low levels
 
macrovascular vessel beds
 
membrane-bound VEGF receptors
 
organ-specific VEGF
 
pathologic angiogenic stimulus
 
peripheral neuropathy
 
positive feedback loops
 
soluble form
 
systemic VEGF levels
 
undergoing evaluation
 
VEGF levels act
 
VEGF receptor levels
 

Barbara Wirostko