May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
2-Methoxyestradiol Subconjunctival Implant in a Model of Choroidal Neovascularization
M.R. Robinson; P. Yuan; J. Baffi; G. Byrnes; H. Kim; R. Lutz; D. Fortman; K.G. Csaky
Author Affiliations & Notes
  • M.R. Robinson
    Bldg 10 Room 10N 112, National Eye Institute, NIH, Bethesda, MD, United States
  • P. Yuan
    Bldg 10 Room 1D51, Clinical Center Pharmacy, NIH, Bethesda, MD, United States
  • J. Baffi
    Bldg 10 Room 1D51, Clinical Center Pharmacy, NIH, Bethesda, MD, United States
  • G. Byrnes
    Bldg 10 Room 1D51, Clinical Center Pharmacy, NIH, Bethesda, MD, United States
  • H. Kim
    Bldg 13 Room 3W10, Division of Bioengineering and Physical Sciences, NIH, Bethesda, MD, United States
  • R. Lutz
    Bldg 13 Room 3W10, Division of Bioengineering and Physical Sciences, NIH, Bethesda, MD, United States
  • D. Fortman
    Bldg 13 Room 3W10, Division of Bioengineering and Physical Sciences, NIH, Bethesda, MD, United States
  • K.G. Csaky
    Bldg 13 Room 3W10, Division of Bioengineering and Physical Sciences, NIH, Bethesda, MD, United States
  • Footnotes
    Commercial Relationships  M.R. Robinson, None; P. Yuan, None; J. Baffi, None; G. Byrnes, None; H. Kim, None; R. Lutz, None; D. Fortman, None; K.G. Csaky, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 3943. doi:
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      M.R. Robinson, P. Yuan, J. Baffi, G. Byrnes, H. Kim, R. Lutz, D. Fortman, K.G. Csaky; 2-Methoxyestradiol Subconjunctival Implant in a Model of Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3943.

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Abstract

Abstract: : Purpose: Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) is a frequent cause of central vision loss in the United States. The angiogenesis inhibitor 2-methoxyestradiol (2ME2) is an endogenous metabolite of estradiol that shows promise in treating CNV. The goal of this study is to evaluate the efficacy of a 2ME2 subconjunctival implant placed in a rat model of CNV. Methods: The 2ME2 implants used a compressed 2ME2 pellet with a diameter of 1.5 mm and a thickness of 1 mm. The pellets were coated with a 20% (w/v) hydroxypropyl cellulose (HPC) solution. A model of rat CNV was done using a previously described Ad-VEGF/CNV model. The implants were inserted into the subconjunctival space of twenty-four Brown Norway rats at the same time an Ad-VEGF subretinal injection was performed to stimulate CNV production. The animals were sacrificed up to two weeks post implantation and the eyes were evaluated histologically for CNV. In vitro release rates were performed by placing the 2ME2 implants in PBS and measuring the drug concentrations over time by HPLC every 24-48 hours, each time replacing the PBS to simulate sink conditions. Results: Twelve rats received 2ME2 implants and twelve rats received sham implants (no drug). Half of the rats were sacrificed after one week and the other half after two. The subconjunctival 2ME2 implants reduced CNV by ~50% at one week but had no effect at two weeks (Table). NUMBER OF EYES WITH CNV In vitro release rates in PBS showed a burst of drug at the initial assay and further assays were not possible because the cellulose-based implant dissolved rapidly. In vivo, the implants were not grossly visible after 1-week. Conclusions: Trans-scleral delivery of 2ME2 using a subconjunctival implant was effective in a rat CNV model at 1-week. A longer release implant is being evaluated to potentially yield a more effective long-term response in the CNV model.  

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Keywords: pharmacology • age-related macular degeneration • choroid: neovascularization 
© 2003, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2015 Association for Research in Vision and Ophthalmology.
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