Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Transplantation of human iPSC-derived photoreceptor precursors in the cone-dominant northern tree shrew
Author Affiliations & Notes
  • Ching tzu Yu
    Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Sangeetha Kandoi
    Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, United States
  • Hannah Follett
    Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Ramesh Periasamy
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Eeshika Mitra
    Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, United States
  • Phyllis Summerfelt
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Susan Freling
    Max Planck Florida Institute for Neuroscience, Jupiter, Florida, United States
  • Joseph Carroll
    Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
    Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Deepak A Lamba
    Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States
    Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Ching tzu Yu None; Sangeetha Kandoi None; Hannah Follett None; Ramesh Periasamy None; Eeshika Mitra None; Phyllis Summerfelt None; Susan Freling None; Joseph Carroll AGTC, Code F (Financial Support), MeiraGTx, Code F (Financial Support), Translational Imaging Innovations, Code I (Personal Financial Interest), Translational Imaging Innovations, Code P (Patent); Deepak Lamba None
  • Footnotes
    Support  T32EY014537, U24EY029891, UL1TR001436, S10OD030229, All May See Foundation BrightFocus Foundation for Macular Degeneration M2023005F
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 3824. doi:
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    • Get Citation

      Ching tzu Yu, Sangeetha Kandoi, Hannah Follett, Ramesh Periasamy, Eeshika Mitra, Phyllis Summerfelt, Susan Freling, Joseph Carroll, Deepak A Lamba; Transplantation of human iPSC-derived photoreceptor precursors in the cone-dominant northern tree shrew. Invest. Ophthalmol. Vis. Sci. 2024;65(7):3824.

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

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Abstract

Purpose : To compare the survival and integration of human induced pluripotent stem cell (hiPSC) derived photoreceptors in tree shrew (Tupaia belangeri) (TS) damage models.

Methods : A total of 12 TS eyes were prepared for transplantation in three models: experimental retinal detachment (n=6), ATP injection (n=4), and undamaged (n=2). ATP-induced damage was created with one intravitreal injection of 5 μl of 0.0085-0.01M ATP. Retinal detachment was created with a subretinal injection of 40-50 μl of 0.9% normal saline. All damage was created at least two weeks prior to cell injections. GFP-expressing hiPSC cone-rich retinal organoids were differentiated for 60 days followed by Notch pathway inhibitor for 24 hours. Cells were dissociated from the organoids with papain and then injected in to the subretinal space of the eye (~0.7-1 million/eye). All animals were treated with immunosuppression from one week prior until the end of the experiment using a combination of cyclosporin A, basiliximab, methylprednisolone, doxycycline, sirolimus, and azathioprine. The injected cells were imaged weekly with fluorescence SLO and OCT. AOSLO imaging was done in select eyes of each group before the last time point (6-8 weeks). Eyes were then enucleated, processed and evaluated with immunohistochemistry (IHC) with GFP (reporter), HuNu (human-specific maker), and OTX2 (photoreceptor).

Results : Nine of 12 eyes (4 detached, 3 ATP damaged, 2 undamaged) showed survival (persistent GFP signal on fluorescence SLO) up to 8 weeks post-injection. Three injections failed due to vitreous reflux. Cross-sectional OCT scans confirmed the injected cells were located in the subretinal space. AOSLO imaging of the GFP-positive region of the select eyes in each group showed the presence of reflective structures of unknown origin. IHC analysis confirmed GFP+ human cells colocalized with the HuNu and OTX2.

Conclusions : This study demonstrated the survival of hiPSC-derived photoreceptor precursors in the cone-dominant northern tree shrew for up to 8 weeks in the subretinal space. Further assessments are needed to compare retinal function pre- and post-injection.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

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