Purchase this article with an account.
Tamim Qaum, Qingwen Xu, Antonia M. Joussen, Mark W. Clemens, Wenying Qin, Kazuaki Miyamoto, Haroutioun Hassessian, Stanley J. Wiegand, John Rudge, George D. Yancopoulos, Anthony P. Adamis; VEGF-initiated Blood–Retinal Barrier Breakdown in Early Diabetes. Invest. Ophthalmol. Vis. Sci. 2001;42(10):2408-2413.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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/Fc construct (VEGF TrapA40). An inactive
IL6 receptor/Fc 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
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
TrapA40, 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.
This PDF is available to Subscribers Only