iPSC-RPE patch restores photoreceptors and regenerates choriocapillaris in a pig retinal degeneration model.

Journal: JCI insight
Published Date: May 22, 2025

Abstract

Dry age-related macular degeneration (AMD) is a leading cause of untreatable vision loss. In advanced cases, retinal pigment epithelium (RPE) cell loss occurs alongside photoreceptor and choriocapillaris degeneration. We hypothesized that an RPE-patch would mitigate photoreceptor and choriocapillaris degeneration to restore vision. An induced pluripotent stem cell-derived RPE (iRPE) patch was developed using a clinically compatible manufacturing process by maturing iRPE cells on a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold. To compare outcomes, we developed a surgical procedure for immediate sequential delivery of PLGA-iRPE and/or PLGA-only patches in the subretinal space of a pig model of laser-induced outer retinal degeneration. Deep learning algorithm-based optical coherence tomography (OCT) image segmentation verified preservation of the photoreceptors over the areas of PLGA-iRPE-transplanted retina and not in laser-injured or PLGA-only-transplanted retina. Adaptive optics imaging of individual cone photoreceptors further supported this finding. OCT-angiography revealed choriocapillaris regeneration in PLGA-iRPE- and not in PLGA-only-transplanted retinas. Our data, obtained using clinically relevant techniques, verified that PLGA-iRPE supports photoreceptor survival and regenerates choriocapillaris in a laser-injured pig retina. Sequential delivery of two 8 mm2 transplants allows for testing of surgical feasibility and safety of the double dose. This work allows one surgery to treat larger and noncontiguous retinal degeneration areas.

Authors

  • Rohan Gupta
    Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Shahbad Daulatpur, Bawana Road, Delhi, 110042, India.
  • Irina Bunea
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Bruno Alvisio
    BioTeam, Life Sciences IT Consulting, Middleton, Massachusetts, USA.
  • Francesca Barone
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Rishabh Gupta
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Dara Baker
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Haohua Qian
    Visual Function Core and.
  • Elena Daniele
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Casey G Contreary
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Jair Montford
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Ruchi Sharma
    University of Victoria Faculty of Engineering & Computer Science, 3800 Finnerty Road, Victoria, British Columbia, V8W 3P6, CANADA.
  • Arvydas Maminishkis
    Ocular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health (NIH).
  • Mandeep S Singh
    Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA singhcorrespauth@gmail.com.
  • Maria Teresa Magone De Quadros Costa
    Consult Services Section, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Amir H Kashani
    Department of Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA.
  • Juan Amaral
    Translational Research Core, National Eye Institute, NIH, Bethesda, Maryland, USA.
  • Kapil Bharti
    Ocular and Stem Cell Translational Research Section, National Eye Institute, NIH, Bethesda, Maryland, USA.

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