May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Effect of Controtostatin on Development of Choroidal Neovascularization in Rats
Author Affiliations & Notes
  • M.E. Mahmoud
    Ophthalmology, Doheny Eye Institute, Retina Institute, USC, Los Angeles, CA
  • S.D. Swenson
    Biochemistry, Cancer Research Laboratory, USC, Los Angeles, CA
  • J. Rossi
    Ophthalmology, Doheny Eye Institute, Retina Institute, USC, Los Angeles, CA
  • S. Sadda
    Ophthalmology, Doheny Eye Institute, Retina Institute, USC, Los Angeles, CA
  • F.K. Costa
    Biochemistry, Cancer Research Laboratory, USC, Los Angeles, CA
  • F.S. Markland Jr
    Biochemistry, Cancer Research Laboratory, USC, Los Angeles, CA
  • E. de Juan
    Ophthalmology, Doheny Eye Institute, Retina Institute, USC, Los Angeles, CA
  • Footnotes
    Commercial Relationships  M.E. Mahmoud, None; S.D. Swenson, None; J. Rossi, None; S. Sadda, None; F.K. Costa, None; F.S. Markland Jr, Pivotal Bioscience, Inc E; E. de Juan, None.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3579. doi:
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      M.E. Mahmoud, S.D. Swenson, J. Rossi, S. Sadda, F.K. Costa, F.S. Markland Jr, E. de Juan; Effect of Controtostatin on Development of Choroidal Neovascularization in Rats . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3579.

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

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Abstract

Abstract: : Purpose: Integrins are cell surface proteins that interact with the extracellular matrix and relay information from the outside of the cell to the inside. Controtostatin (CN) is a homodimeric disintegrin that inhibits integrin function by binding via its tri–peptide RGD sequence. Angiogenesis is a complex process that requires extracellular matrix; CN affects the development of angiogenesis. The aim of the present study is to investigate the effect of CN on the development of laser–induced choroidal neovascularization (CNV) in a Brown Norway rat model. Methods: Eighty–one male Brown Norway rats were divided into 2 study groups: a pharmacokinetic group (41 rats) and an efficacy group (40 rats). In the pharmacokinetic group, 21 rats were used as controls and 20 rats for the CNV model. Liposomes loaded I125CN was injected I.V. at a dose of 200 ug/rat. Animals were subdivided into 7 subgroups of 3 rats each except one subgroup of the CNV model, which contained only 2 rats. Blood and tissues were collected from the rats at 7 different time points after CN injection. Radioactivity of blood and tissues were measured using a gamma counter, and the CN concentrations were deduced from the specific activity of the injected CN. The rats in the efficacy study were divided into 2 groups of 20 rats each. The control group was treated with empty liposomes and the treatment group was treated biweekly with 200 ug/rat of unlabelled and liposomal CN. The first dose of CN was given I.V.; the remaining doses were given SC. The CN and liposome treatment started 1 hour before the bilateral induction of CNV by laser. Development of CNV was monitored after 2 weeks by fluorescein angiography and histopathologic study.Results: I125CN exhibited a two–compartmental model decay in both the control and the CNV rats. In control rats, the half–lives of the central and elimination compartments were 8 min and 8.1 hours, respectively. The half life of distribution of CN into the control eyes was 1.52 min, and the time to reach the maximum concentration (Tmax) was 14.5 min. The parameter values of the CNV rats were close to the control values. CN had a small (5%) but significant decrease (P< 0.05) the incidence of CNV development when compared to the controls.Conclusions: Iodine125 allows reliable detection of CN in different tissues, and the liposome carrier facilitated intraocular penetration and retarded systemic elimination. CN inhibited the development of CNV by 5%; although this is significant, it may not be clinically translatable.

Keywords: choroid: neovascularization • extracellular matrix • laser 
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