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Xiaorong Li; The protective effects of a novel recombinant decoy receptor targeting both VEGF and EGF on retinas of diabetic rats. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5796.
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© ARVO (1962-2015); The Authors (2016-present)
The innovative drug VF28 is a recombinant decoy receptor that can bind to VEGF and FGF with specificity and high affinity. This study aimed to examine the protection of VF28 from retinal damage in retinas of streptozotocin (STZ)-induced diabetic rats.
Sprague Dawley rats were intravenously injected with STZ to induce diabetes. At week 5 and 9 following diabetic induction, the rats were intravitreally injected with the VF 28 (2, 6,18 µg), FGF trap (12 µg), or VEGF trap (12 µg), and the rats in control groups were injected with normal saline. At week 12 after diabetic induction, Evans blue assay was performed to examine blood-retinal barrier breakdown and retinal vascular leakage; trypsin digestion followed by PAS staining was used to detect acellular capillary structures; electron microscopy was employed to examine thickening of retinal capillary basement membrane; western blots were used to detect protein expression changes of FGF, VEGF, and FLK in the rat retinas.
VF28 at each dosage, VEGF trap, and FGF trap all ameliorated the retinal vascular leakage in the diabetic rats; VF28, VEGF trap, and FGF trap alleviated acellular capillary structures and capillary basement membrane thickening in diabetic retinas, VF28 at high dosage has the most significant protective effects among these experimental groups. Western blots showed that VEGF and FGF protein levels were significantly up-regulated in the DM retinas compared to the normal controls; VF 28 at all doses significantly reduced the VEGF protein levels, whereas VF 28 at high dose significantly downregulated FGF protein expression. VEGF trap and FGF trap significantly reduced the protein levels of their respective targets. Besides, FLK levels were significantly diminished in the DM retinas, which was dose-dependently elevated in the VF28 groups and recovered to the normal levels in the VE28 medium and high dose groups.
In the STZ-induced diabetic rat model, VF28, at the optimal dosage, was superior to VEGF rap and FGF trap in ameliorating retinal vascular leakage, improving retinal acellular capillary structures and thickening of capillary basement membrane. The protective effects of VF28 may be ascribed to maintaining the normalized VEGF and FGF expression levels and their signaling transductions in the diabetic retinas.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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