Effect of Conjunctival Ring with Dexamethasone Sodium Phosphate on Rabbit VEGF-induced Blood-Retinal Barrier Breakdown.

Abstract

Purpose : The conjunctival ring (CR) is a novel device designed for drug delivery to the posterior segment of the eye. Previously, we reported the safety of the CR containing dexamethasone sodium phosphate (DSP) in mice and rabbits (ARVO 2014). The aim of this study was to evaluate the inhibitory effect of the CR containing DSP on VEGF-induced blood-retinal barrier (BRB) breakdown model.

Methods : Male Japanese white rabbits anesthetized with sevoflurane inhalation and topical 0.4% oxybuprocaine hydrochloride. Five-hundred ng VEGF was injected into the vitreous. After awakening, CR immersed in 0.2% or 0.6% DSP was placed on the right eye of rabbit for 2 days (8 hours per day). As a control, 0.1% DSP solution was topically administrated to the right eye of rabbit 4 times a day. Two days after the injection of VEGF, retinal vasculopathy was assessed with fundus photography. Sodium fluorescein (50 mg/kg in 1 mL saline) was injected via the marginal ear vein. One hour after the injection of fluorescein, animals were euthanized. Eyes were enucleated and frozen. Vitreous bodies were isolated from the eyes and then, the vitreous concentration of fluorescein was measured by fluorescence microplate-reader.

Results : VEGF-injection markedly induced the retinal vasodilation. VEGF-injection induced an 8.2 fold increase of vitreous fluorescein concentration, compared with vehicle-injection (VEGF -injection group: 1723 ± 275.8 ng/mL, vehicle-injection: 210.6 ± 90.9 ng/mL). CR-0.2%DSP, CR-0.6%DSP and Solution-0.1%DSP significantly blocked BRB breakdown by 83%, 83% and 73%, respectively (P<0.01). Total DSP dose of CR-0.2%DSP (about 100 μg/day/eye) was lower than that of Solution-0.1%DSP (200 μg/day/eye); however, CR-0.2%DSP showed a tendency to be more effective than Solution-0.1%DS on suppressing BRB breakdown.

Conclusions : Our data suggested that the CR effectively delivered DSP to the retina compared with ophthalmic solution. The CR is a useful device for treatment of posterior segment diseases.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.