May 2003
Volume 44, Issue 13
ARVO Annual Meeting Abstract  |   May 2003
Rapamycin Inhibits Choroidal Neovascularization
Author Affiliations & Notes
  • R. Wen
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, United States
  • Z. Wang
    Department of Eye Trauma, Zhongshan Ophthalmic Center, Guangzhou, China
  • Y. Song
    Department of Eye Trauma, Zhongshan Ophthalmic Center, Guangzhou, China
  • L. Zhao
    Department of Eye Trauma, Zhongshan Ophthalmic Center, Guangzhou, China
  • Y. Liu
    Department of Eye Trauma, Zhongshan Ophthalmic Center, Guangzhou, China
  • A.M. Laties
    Department of Eye Trauma, Zhongshan Ophthalmic Center, Guangzhou, China
  • Z. Luo
    Departments of Medicine and Biochemistry, Boston University, Boston, MA, United States
  • Footnotes
    Commercial Relationships  R. Wen, None; Z. Wang, None; Y. Song, None; L. Zhao, None; Y. Liu, None; A.M. Laties, None; Z. Luo, None.
  • Footnotes
    Support  NIH Grant EY12727, the Foundation Fighting Blindness, the Karl Kirchgessner Foundation.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 3928. doi:
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      R. Wen, Z. Wang, Y. Song, L. Zhao, Y. Liu, A.M. Laties, Z. Luo; Rapamycin Inhibits Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3928.

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

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Abstract: : Purpose: Rapamycin (sirolimus) is a macrocyclic lactone isolated from Streptomyces hygroscopicus. Clinically, it is used for immunosuppression. Rapamycin binds to FK Binding Protein-12 (FKBP-12) to form a Rapamycin-FKBP-12 complex, which binds to and inhibits the activity of mTOR (mammalian target of rapamycin). Rapamycin was found to inhibit VEGF expression and also inhibit response of vascular endothelial cells to VEGF. We report here that rapamycin inhibits choriodal neovascularization (CNV) in a subretinal Matrigel deposit model of CNV. Methods: Experimental CNV was induced by injection of 1.2 µl Matrigel to the subretinal space of adult Sprague-Dawley rats through a 33-gauge needle. Rapamycin was administrated either as a suspension in the Matrigel (2.5 µg/µl) and injected with Matrigel to the subretinal space (in-gel delivery), or orally at a dose of 2.5 mg/kg/day (starting 2 days before Matrigel injection). Animals were sacrificed 10 days after Matrigel injection by CO2 inhalation and perfused with Vessel Paint, followed by 4% paraformaldehyde. The anterior portion of the eye was removed and the eyecup was embedded in 5% agarose. Serial thick sections (100 µm) were cut on a vibratome and were examined by fluorescence microscopy for neovascularization in the Matrigel deposit. Serial optical sections were obtained using confocal microscopy and 3-D images of CNV were reconstructed. Results: Neovascularization was observed in all control eyes. New vessels originated from choriocapillaries and ramified in the subretinal Matrigel deposits. In contrast, no neovascularization was found in any of the eyes treated with rapamycin. Conclusions: Rapamycin, delivered either locally or systemically, inhibits CNV development. Local administration of rapamycin could be a worthwhile approach to the treatment of CNV to avoid potential systemic adverse effects.

Keywords: choroid: neovascularization • age-related macular degeneration • neovascularization 

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