July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Survival and migration of photoreceptor precursors following transplantation into a macaque eye with host photoreceptors ablated
Author Affiliations & Notes
  • Ebrahim Aboualizadeh
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • M Joseph Phillips
    Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
    McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Jennifer Strazzeri
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • David Diloreto
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • Kamal Dhakal
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Brittany Bateman
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • Jennifer J Hunter
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • William H Merigan
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • David M Gamm
    Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
    Department of Ophtalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • David R Williams
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    The Institute of Optics, University of Rochester, Rochester, New York, United States
  • Footnotes
    Commercial Relationships   Ebrahim Aboualizadeh, None; M Joseph Phillips, Opsis therapeutics (I), Opsis therapeutics (C); Jennifer Strazzeri, None; David Diloreto, None; Kamal Dhakal, None; Brittany Bateman, None; Jennifer Hunter, None; William Merigan, None; David Gamm, Opsis therapeutics (I), Opsis therapeutics (C), Opsis therapeutics (P), Opsis therapeutics (S); David Williams, University of Rochester (P), Warby Parker (F)
  • Footnotes
    Support  Research reported in this publication was supported by the National Eye Institute of the National Institutes of Health under Awards No. U01EY025497 and No. P30 EY001319. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Inst. of Health. This study was supported by an Unrestricted Grant to the University of Rochester, Department of Ophthalmology from Research to Prevent Blindness, New York, New York.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6397. doi:https://doi.org/
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    • Get Citation

      Ebrahim Aboualizadeh, M Joseph Phillips, Jennifer Strazzeri, David Diloreto, Kamal Dhakal, Brittany Bateman, Jennifer J Hunter, William H Merigan, David M Gamm, David R Williams; Survival and migration of photoreceptor precursors following transplantation into a macaque eye with host photoreceptors ablated. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6397. doi: https://doi.org/.

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

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Abstract

Purpose : Non-human primates have the potential to be a highly informative model for stem cell-based vision restoration. In a new laser lesion model of macaque photoreceptor loss, we investigated donor photoreceptor survival and migration following transplantation in the subretinal space of macaque eyes.

Methods : In a 4-year-old female macaque, nine perifoveal lesions with localized damage to the photoreceptor layer were created using femtosecond pulses delivered through adaptive optics (730 nm, 55 fs, 80 MHz, 0.81° × 0.73°). Immune suppression was provided by a subcutaneous injection of cyclosporine and an oral prednisone. Fluorescently-labeled photoreceptor precursors (CRX+/tdTomato) derived from WA09 human embryonic stem cells were transplanted subretinally, raising two blebs, one containing all nine lesions and one in a lesion-free region. Donor cells were monitored noninvasively between six days and three months post-transplantation using fluorescence (λExcitation: 561 nm; λEmission: 580-676 nm) adaptive optics scanning light ophthalmoscopy (AOSLO), SLO, and OCT (Heidelberg Spectralis). Immunohistochemical examination was then performed.

Results : We observed individual donor cells and cell clusters in both blebs. Fluorescence AOSLO imaging showed that the area of a cell cluster in the bleb with lesions decreased 25% after 4 weeks and 65% after 10 weeks. The area of cell clusters in the non-lesioned retina decreased 50% (±5%) after 4 weeks, and 80% (±7%) 10 weeks post-transplantation. In the non-lesioned retina, immunohistochemistry did not show any evidence of migration of donor cells; however, in the lesioned retina some cells migrated into the outer plexiform layer and sent processes toward the inner retina.

Conclusions : This finding suggests that laser ablation disrupts an anatomical barrier posed by the host photoreceptor layer resulting in donor cell migration toward the bipolar cell layer, an important step toward establishing functional connectivity. The progressive loss of donor cells post-transplantation remains a challenge to vision restoration. The ability of adaptive optics retinal imaging to monitor over months fluorescently-labeled donor cells at the celular scale could accelerate the development of methods to improve donor cell survival and integration.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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