September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The HIF-1 inhibitor acriflavine is visualized in retina after multiple modes of administration/doses that suppress ocular neovascularization
Author Affiliations & Notes
  • Ji-kui Shen
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Mingbing Zeng
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Kun Ding
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Lucy Lu
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Raquel Formica
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Yuanyuan Liu
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Sean Hackett
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Peter A Campochiaro
    Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Ji-kui Shen, None; Mingbing Zeng, None; Kun Ding, None; Lucy Lu, None; Raquel Formica, None; Yuanyuan Liu, None; Sean Hackett, None; Peter Campochiaro, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4537. doi:
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    • Get Citation

      Ji-kui Shen, Mingbing Zeng, Kun Ding, Lucy Lu, Raquel Formica, Yuanyuan Liu, Sean Hackett, Peter A Campochiaro; The HIF-1 inhibitor acriflavine is visualized in retina after multiple modes of administration/doses that suppress ocular neovascularization. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4537.

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

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Abstract

Purpose : Acriflavine is a fluorescent molecule that has antibacterial and antiviral activities, and recently has been demonstrated to block HIF-1 transcriptional activity. In this study, we sought to explore visualization of acriflavine in the retina and anti-angiogenic activity after different modes of administration.

Methods : Fluorescence microscopy was used to visualize acriflavine at several times after intraocular injection, suprachoroidal injection, or topical administration. Effect on HIF-1-induced gene expression and retinal neovascularization (NV) was tested in mice with oxygen-induced ischemic retinopathy. Effect on choroidal NV was tested in mice or rats with laser-induced rupture of Bruch’s membrane.

Results : Acriflavine fluorescence was present in the inner retina 1 hour after intraocular injection of 10ng, was intense and throughout the entire retina at 6 and 24 hours after injection, and was still detectable 5 days after injection. After suprachoroidal injection of 300ng in rats, acriflavine fluorescence was seen first in the outer retina and at 24 hours half the retina fluoresced with a gradient from peripheral (injected side) to posterior retina. At 5 days, fluorescence was seen throughout the entire choroid with little in the retina. Dose-response and time course studies showed fluorescence detectable in the outer retina at 5 minutes and throughout the entire retina at 1 hour after administration. After a single 10% drop, bright fluorescence was present at 6 hours and faint fluorescence was present at 12 hours. Intravitreous injection of 10 or 50 ng of Acriflavine effectively inhibited expression of the HIF-1-responsive genes Vegf, Pdgfb and Angpt2 and strongly suppressed retinal NV. Multiple routes of acriflavine administration significantly suppressed choroidal NV including subcutaneous injection (5mg/kg), intravitreous injection (100ng), suprachoroidal injection (300ng), and topical (0.1% twice a day).

Conclusions : This study confirms the critical role of HIF-1 in retinal and choroidal NV and demonstrates that acriflavine provides a valuable tool to study delivery to the retina by different modes of administration and pharmacodynamics.

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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