June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A novel minimally invasive adjustable-depth blunt injector for delivery of therapeutics into the extravascular spaces of the choroid
Author Affiliations & Notes
  • Ygal Rotenstreich
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
    Goldschleger Research Institute, Tel Aviv University, Tel Aviv, Israel
  • Adi Tzameret
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
    Goldschleger Research Institute, Tel Aviv University, Tel Aviv, Israel
  • Sapir Kalish
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
    Goldschleger Research Institute, Tel Aviv University, Tel Aviv, Israel
  • Ettel Bubis
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
    Goldschleger Research Institute, Tel Aviv University, Tel Aviv, Israel
  • Michael Belkin
    Goldschleger Research Institute, Tel Aviv University, Tel Aviv, Israel
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
  • Iris Moroz
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
  • Mordechai Rosner
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
    Goldschleger Research Institute, Tel Aviv University, Tel Aviv, Israel
  • Itay Levy
    Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Ramat Gan, Israel
  • Shlomo Margel
    Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Ramat Gan, Israel
  • Ifat Sher-Rosenthal
    Goldschleger Eye Institute , Sheba Medical Center, Tel Hashomer, Israel
  • Footnotes
    Commercial Relationships   Ygal Rotenstreich, Sheba Medical Center (P); Adi Tzameret, None; Sapir Kalish, None; Ettel Bubis, None; Michael Belkin, None; Iris Moroz, None; Mordechai Rosner, None; Itay Levy, None; Shlomo Margel, None; Ifat Sher-Rosenthal, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4760. doi:
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      Ygal Rotenstreich, Adi Tzameret, Sapir Kalish, Ettel Bubis, Michael Belkin, Iris Moroz, Mordechai Rosner, Itay Levy, Shlomo Margel, Ifat Sher-Rosenthal; A novel minimally invasive adjustable-depth blunt injector for delivery of therapeutics into the extravascular spaces of the choroid. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4760.

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

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Abstract

Purpose : To investigate the feasibility and safety of a novel minimally-invasive adjustable-depth blunt injector for pharmaceuticals and cell therapy delivery into the extravascular spaces of the choroid (EVSC).

Methods : An adjustable-depth blunt injector for delivery of therapeutics into the EVSC was developed. Two hundred and fifty microliters containing Indocyanine Green (ICG), sodium fluorescein, iron oxide nanoparticles (IONPs) or 15 million human bone marrow mesenchymal stem cells (hBMSCs) were injected into the EVSC of New Zealand rabbits using the novel injector, 3.5 mm posterior to the limbus. No immunosuppressants were used. Spectral Domain Optical Coherence Tomography (SD-OCT), fundus imaging, electroretinography (ERG) and histology analysis were performed for assessment of injection safety and efficacy.

Results : ICG, fluorescein, IONPs and stem cells were detected across the EVSC in rabbit eyes, covering over 80 percent of the posterior eye surface. Injected IONPs were retained in the EVSC for at least two weeks following injection. Stem cells were retained in the EVSC for 10 weeks following transplantation. No retinal detachment, choroidal hemorrhage or inflammation were detected in any of the injected eyes or contralateral control eyes. No reduction in retinal function was recorded by electroretinogram up to 10 week following cell transplantation.

Conclusions : This novel minimally invasive delivery system may be used to safely inject large volumes of pharmaceuticals and cell therapies into the EVSC from the same location used for intravitreal injections. Therapeutics are introduced into a new treatment reservoir compartment -the EVSC which can serve as a depot, in close proximity to the retinal pigment epithelium (RPE), throughout the surface of the RPE. This system is predicted to enhance the therapeutic effects of treatments for posterior eye disorders. Furthermore, this study demonstrates the safety of hBMSC transplantation in the EVSC compartment and is expected to directly lead to phase I/II clinical trials for hBM-MSC transplantation in retinal degeneration patients.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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