May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Functional Characterization of the MMP–derived Endostatin–spanning Degradation Products of Type XVIII Collagen
Author Affiliations & Notes
  • J.–H. Chang
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • J.A. Javier
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • G.–Y. Chang
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • H.B. Oliveira
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • E.F. Jarade
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • A. Yu
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • E. Albe
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • D.T. Azar
    Ophthalmology, Mass Eye and Ear Infirmary, Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships  J. Chang, None; J.A. Javier, None; G. Chang, None; H.B. Oliveira, None; E.F. Jarade, None; A. Yu, None; E. Albe, None; D.T. Azar, None.
  • Footnotes
    Support  NIH grant EY014048
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 4813. doi:
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      J.–H. Chang, J.A. Javier, G.–Y. Chang, H.B. Oliveira, E.F. Jarade, A. Yu, E. Albe, D.T. Azar; Functional Characterization of the MMP–derived Endostatin–spanning Degradation Products of Type XVIII Collagen . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4813.

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

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Abstract

Abstract: : Purpose: To demonstrate the effect of the MT1–MMP derived 23 kDa endostatin–spanning fragment of type XVIII collagen on corneal neovascularization using gene therapy techniques. Methods:We have reported that the NC terminal region of type XVIII collagen can be cleaved by the matrix metalloproteinase, matrilysin (MMP–7), to generate an endostatin spanning 28 kDa fragment with endostatin like anti–angiogenic properties. We have recently generated a new endostatin spanning molecule by cleaving recombinant human NC1 fragments of type XVIII collagen with MT1–MMP. The recombinant NC1 fragments were purified and incubated with various concentrations of MT1–MMP. Constructs of endostatin, the 28 kDa endostatin spanning fragment, and the MT1–MMP derived 23 kDa endostatin spanning fragment were generated using a MYC tagged pEF vector. A corneal neovascularization model using C57BL/6 mice implanted with 80 ng bFGF pellets were treated with intra–corneal injections of these endostatin–containing plasmid constructs Results:Degradation products from the exposure of recombinant NC1 fragments to MT1–MMP were sequenced and found to be identical with previously published data. There was significant reduction in the bFGF induced corneal neovascularization in corneas treated with intra–corneal injections of MYC tagged pEF vectors containing endostatin, the 28 kDa and 23 kDa endostatin spanning fragments as compared to that of the MYC tagged pEF vector alone Conclusions: MMP–7 and MT1–MMP derived endostatin spanning fragments can diminish bFGF induced corneal neovascularization in mice.

Keywords: cornea: basic science • wound healing • extracellular matrix 
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