Purchase this article with an account.
Nikita Ved, Richard Hulse, Lucy Donaldson, James Bainbridge, David Bates; VEGF165b reduces blood vessel permeability in diabetic retinas. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2705.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Vascular hyperpermeability in diabetic macular edema (DME) is associated with upregulation of pro-angiogenic vascular endothelial growth factor (VEGF). VEGF165 has been associated with degradation of tight-junction proteins ZO1 and occludin in vitro. This reorganisation of ZO1 and occludin is prevented in RPE cells by co-treatment with VEGF165b, an alternatively spliced anti-angiogenic isoform, suggesting that VEGF165b could abrogate retinal vascular hyperpermeability. The aim of this study was to determine whether VEGF165b reduces retinal vascular hyperpermeability in rats with streptozotocin-induced diabetes.
Sprague-Dawley male rats (200g) were induced with diabetes using streptozotocin (50mg/kg). After 6 days, 5µl saline was injected into one eye of each diabetic rat, and 5µl 10ng/µl rhVEGF165b injected into the contralateral eye. Control rats had no injection in one eye, and 5µl saline in the other eye. On day 7, Evans blue (45mg/kg) was injected i.v into anaesthetised rats. Plasma was collected every 15 minutes for 2 hours, after which, animals were sacrificed and eyes enucleated and retinas excised. Retinas were weighed and Evans blue was extracted using formamide, with Evans blue solute flux calculated from the amount of Evans blue, per wet weight of tissue, per hour relative to the mean plasma Evans blue level during the 2 hr perfusion.
Increased solute flux in the retinae of rats with streptozotocin-induced diabetes was significantly reduced by intraocular administration of rhVEGF165b compared with vehicle-injected controls (P<0.05). Vehicle-treated eyes showed no significant difference in solute flux compared to uninjected eyes in control rats.
VEGF165b reduces retinal vascular hyperpermeability in streptozotocin-induced diabetes in rats and may offer an effective therapeutic approach to diabetic retinopathy.
This PDF is available to Subscribers Only