VEGF-initiated blood-retinal barrier breakdown in early diabetes.


PURPOSE The objectives of this study were to (1) determine whether endogenous vascular endothelial growth factor (VEGF) triggers diabetic blood-retinal barrier breakdown, and (2) identify the site as well as phenotype of the hyperpermeable diabetic retinal vessels. METHODS Retinal VEGF mRNA levels were quantified in 1-week diabetic rats using the RNase protection assay. VEGF bioactivity was blocked via the systemic administration of a highly specific VEGF-neutralizing soluble Flt/F(c) construct (VEGF TrapA(40)). An inactive IL6 receptor/F(c) construct (IL6R Trap) was used as an isotype control. Blood-retinal barrier breakdown was quantified using the Evans blue technique and was spatially localized with fluorescent microspheres. RESULTS Retinal VEGF mRNA levels in 1-week diabetic animals were 3.2-fold higher than in nondiabetic controls (P < 0.0001). Similarly, retinal vascular permeability in 8-day diabetic animals was 1.8-fold higher than in normal nondiabetic controls (P < 0.05). Diabetes-induced blood-retinal barrier breakdown was dose-dependently inhibited with VEGF TrapA(40), with 25 mg/kg producing complete inhibition of the diabetes-induced increases (P < 0.05). Blood-retinal barrier breakdown in diabetic animals treated with solvent alone or IL6R Trap did not differ significantly from untreated diabetic animals (P > 0.05). Spatially, early blood-retinal barrier breakdown was localized to the retinal venules and capillaries of the superficial retinal vasculature. CONCLUSIONS Early blood-retinal barrier breakdown in experimental diabetes is VEGF dependent and is restricted, in part, to the venules and capillaries of the superficial inner retinal vasculature. VEGF inhibition should prove a useful therapeutic approach in the treatment of early diabetic blood-retinal barrier breakdown.

Extracted Key Phrases

3 Figures and Tables

Citations per Year

1,954 Citations

Semantic Scholar estimates that this publication has 1,954 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Qaum2001VEGFinitiatedBB, title={VEGF-initiated blood-retinal barrier breakdown in early diabetes.}, author={Tamim Qaum and Q Xu and Antonia Maria Joussen and Mark W. Clemens and Wenjuan Qin and K-i Miyamoto and Harout Hass{\'e}ssian and Stanley J. Wiegand and John S. Rudge and George D. Yancopoulos and Anthony P. Adamis}, journal={Investigative ophthalmology & visual science}, year={2001}, volume={42 10}, pages={2408-13} }