June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Development of 3D retinal grafts for the treatment of retinal degenerative blindness
Author Affiliations & Notes
  • Laura R Bohrer
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Ian C Han
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Jessica A Cooke
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Erin R Burnight
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Arwin Shrestha
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Department of Biomedical Engineering, University of Iowa, Iowa, United States
  • Louisa Affatigato
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Luke A Wiley
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Kristan Worthington
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Department of Biomedical Engineering, University of Iowa, Iowa, United States
  • Katherine N Gibson-corley
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Robert F Mullins
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Edwin M Stone
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Budd Tucker
    Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States
    Ophthalmology & Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Laura Bohrer, None; Ian Han, None; Jessica Cooke, None; Erin Burnight, None; Arwin Shrestha, None; Louisa Affatigato, None; Luke Wiley, None; Kristan Worthington, None; Katherine Gibson-corley, None; Robert Mullins, None; Edwin Stone, None; Budd Tucker, None
  • Footnotes
    Support  R01EY024605, Elmer and Sylvia Sramek Charitable Foundation, Howard Ruby Chair and Professor of Regenerative Ophthalmology
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2511. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Laura R Bohrer, Ian C Han, Jessica A Cooke, Erin R Burnight, Arwin Shrestha, Louisa Affatigato, Luke A Wiley, Kristan Worthington, Katherine N Gibson-corley, Robert F Mullins, Edwin M Stone, Budd Tucker; Development of 3D retinal grafts for the treatment of retinal degenerative blindness. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2511.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Induced pluripotent stem cell (iPSC)-derived retinal cells hold great promise for restoring vision in patients with retinal degenerative blindness. However, traditional bolus transplantation approaches result in poor cell survival and limited synaptic integration. Tissue engineering scaffold-based strategies, aimed at reducing post-transplant cell death, have potential to overcome these issues. The purpose of this study was to evaluate local and systemic toxicity following transplantation of human iPSC-derived retinal cell grafts in an immune suppressed rat model.

Methods : Polycaprolactone (PCL) scaffolds were generated by injecting a PCL prepolymer solution into a polymerization chamber containing a photomask designed to induce pore formation. Scaffolds were polymerized under UV light, washed and sterilized via gamma irradiation. IPSC derived retinal organoids were generated from 6 patients using a 3D differentiation protocol. Organoids were dissociated and seeded in sterilized PCL scaffolds. Retinal cell grafts were analyzed via immunocytochemistry and 1mm punches were transplanted into the subretinal space of RNU-/- rats (N=210). Full necropsy with complete histopathology, clinical chemistry and hematology were performed at 1-, 3-, and 6-months post-transplantation.

Results : Nine photomasks with 25 to 75μm diameter spots, separated from each other by 25 to 75μm, were designed and fabricated. The photomask with 50μm spots separated by 25μm was ideal for production of consistent PCL scaffolds containing full thickness pores with stable interpore structure. Two weeks after scaffold seeding, iPSC derived photoreceptor precursor cells expressing recoverin were polarized and densely packed in columns throughout the pores, recapitulating the retina. Following subretinal transplantation in RNU-/- rats, retinal reattachment was noted in all eyes, and slow degradation of the biodegradable PCL scaffold was detected via fundoscopy over the duration of the study. No evidence of treatment induced retinal or systemic toxicity/tumorgenicity was detected by gross or histopathologic evaluation, hematology and clinical chemistry.

Conclusions : By using photomasks designed to generate PCL cell delivery scaffolds during photopolymerization, we were able to successfully develop a high-throughput platform for testing of local and systemic toxicity following subretinal transplantation of patient derived retinal cell grafts.

This is a 2020 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×