September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Effect of Conjunctival Ring with Dexamethasone Sodium Phosphate on Rabbit VEGF-induced Blood-Retinal Barrier Breakdown.
Author Affiliations & Notes
  • Hiroaki Takahashi
    Research & Development Division, Senju Pharmaceutical Co., Ltd., Kobe, Hyogo, Japan
  • Wakiko Asayama
    Research & Development Division, Senju Pharmaceutical Co., Ltd., Kobe, Hyogo, Japan
  • Haruka Obata
    Research & Development Division, SEED Co., Ltd., Saitama, Japan
  • Toru Matsunaga
    Research & Development Division, SEED Co., Ltd., Saitama, Japan
  • Atsuhiro Kanda
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Kousuke Noda
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Susumu Ishida
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  • Footnotes
    Commercial Relationships   Hiroaki Takahashi, Senju Pharmaceutical Co., Ltd. (E), Senju Pharmaceutical Co., Ltd. (P); Wakiko Asayama, Senju Pharmaceutical Co., Ltd. (E), Senju Pharmaceutical Co., Ltd. (P); Haruka Obata, SEED Co., Ltd. (E), SEED Co., Ltd. (P); Toru Matsunaga, SEED Co., Ltd. (E), SEED Co., Ltd. (P); Atsuhiro Kanda, Senju Pharmaceutical Co., Ltd. (F); Kousuke Noda, Senju Pharmaceutical Co., Ltd. (F); Susumu Ishida, Senju Pharmaceutical Co., Ltd. (F)
  • Footnotes
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Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3998. doi:
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      Hiroaki Takahashi, Wakiko Asayama, Haruka Obata, Toru Matsunaga, Atsuhiro Kanda, Kousuke Noda, Susumu Ishida; Effect of Conjunctival Ring with Dexamethasone Sodium Phosphate on Rabbit VEGF-induced Blood-Retinal Barrier Breakdown.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3998.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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