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Retinal Pathophysiological Evaluation in a Rat Model
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Advanced glycation end products increase retinal vascular endothelial growth factor expression
1Laboratory for Surgical Research, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
The Journal of Clinical Investigation
|April 29, 1998
Summary
Advanced glycation end products (AGEs) increase vascular endothelial growth factor (VEGF) in the retina. This suggests AGEs contribute to diabetic retinopathy by upregulating VEGF, a key factor in retinal neovascularization.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Diabetic retinopathy is a complication of diabetes, characterized by abnormal blood vessel growth.
- Advanced glycation end products (AGEs) are implicated in diabetic complications.
- Vascular endothelial growth factor (VEGF) plays a critical role in retinal neovascularization.
Purpose of the Study:
- To investigate the pathogenic mechanisms linking AGEs to diabetic retinopathy.
- To determine if AGEs influence VEGF expression in retinal cells.
Main Methods:
- AGEs were administered to rat retinas and cultured human RPE and bovine vascular smooth muscle cells.
- VEGF mRNA and protein levels were measured.
- The effect of antioxidants and hypoxia on AGE-induced VEGF expression was assessed.
- An anti-VEGF antibody was used to block cell proliferation.
Main Results:
- AGEs significantly increased VEGF mRNA in multiple retinal cell layers in vivo.
- AGEs elevated VEGF mRNA and protein secretion in vitro.
- AGE-induced VEGF increases were dose- and time-dependent, inhibited by antioxidants, and additive with hypoxia.
- Neutralization of VEGF blocked AGE-induced endothelial cell proliferation.
Conclusions:
- AGEs promote diabetic retinopathy pathogenesis by increasing retinal VEGF gene expression.
- Targeting AGEs or VEGF may offer therapeutic strategies for diabetic retinopathy.

