The Simultaneous Treatment of MMP-2 Stimulants in Retinal Transplantation Enhances Grafted Cell Migration into the Host Retina

Authors

  • Takuya Suzuki,

    1. Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • Michiko Mandai M.D.,

    Corresponding author
    1. Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan
    • Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan. Telephone: +81-75-751-4717; Fax: +81-75-751-4731
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  • Masayuki Akimoto,

    1. Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan
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  • Nagahisa Yoshimura,

    1. Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • Masayo Takahashi

    1. Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan
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Abstract

The success of functional retinal cell transplantation has been limited by the low efficiency of the transplanted cell integration into the host retina. Given that the extracellular matrix (ECM) is thought to inhibit entry and axonal outgrowth of grafted neural cells into the host retina, modulation of the ECMs in the host environment may overcome this limitation. Here, we demonstrate that matrix metalloprotease-2 (MMP-2) expression is associated with the high migratory potential of adult rat hippocampus-derived neural stem cells compared with retinal progenitor cells. In addition, MMP-2, as well as its reported inducers concanavalin A and 17β-estradiol, can trigger the migration of retinal progenitor cells into explanted retinas. Inhibitors of MMP-2 suppressed these effects. Intense cell migration is not required for photoreceptor transplantation; however, the environment that allows the transplanted cells to integrate is most important. Migration of the transplanted cells is a good index of the acceptance of grafted cell of the host tissue. Strategies modulating the environment by MMP-2 stimulation may provide an advance in the development of retinal transplantation.

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