Investigative Ophthalmology & Visual Science Cover Image for Volume 64, Issue 8
June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Photoreceptor Degeneration Rescue in Dystrophic RCS Rats After hESC-RPE Cell Sub-retinal Transplantation
Author Affiliations & Notes
  • Sandeep Kumar
    Ophthalmology, Pharmaron US Lab Services, San Diego, California, United States
  • Maria Pereira
    Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark
  • Andreas Wrona
    Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark
  • Sara Mangosing
    Ophthalmology, Pharmaron US Lab Services, San Diego, California, United States
  • Anders Kvanta
    St. Erik Eye Hospital, Karolinska Institutet, Solna, Sweden
  • Svetlana Nikoulina
    Ophthalmology, Pharmaron US Lab Services, San Diego, California, United States
  • Helder Andre
    St. Erik Eye Hospital, Karolinska Institutet, Solna, Sweden
  • Fredrik Lanner
    Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden
  • Glenwood G Gum
    Ophthalmology, Pharmaron US Lab Services, San Diego, California, United States
  • Linda Manza
    Ophthalmology, Pharmaron US Lab Services, San Diego, California, United States
  • Carlos Villaescusa
    Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark
  • Dorthe Bach Toft
    Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark
  • Footnotes
    Commercial Relationships   Sandeep Kumar None; Maria Pereira None; Andreas Wrona None; Sara Mangosing None; Anders Kvanta None; Svetlana Nikoulina None; Helder Andre None; Fredrik Lanner None; Glenwood Gum None; Linda Manza None; Carlos Villaescusa None; Dorthe Bach Toft None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3012. doi:
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      Sandeep Kumar, Maria Pereira, Andreas Wrona, Sara Mangosing, Anders Kvanta, Svetlana Nikoulina, Helder Andre, Fredrik Lanner, Glenwood G Gum, Linda Manza, Carlos Villaescusa, Dorthe Bach Toft; Photoreceptor Degeneration Rescue in Dystrophic RCS Rats After hESC-RPE Cell Sub-retinal Transplantation. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3012.

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

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Abstract

Purpose : Morphological and functional changes in the photoreceptors cells are either due to genetic defects or a compromised function of retinal pigment epithelium (RPE) cells. These degenerative changes are progressive and ultimately lead to blindness in humans for which no suitable treatment exists. In this study, we have evaluated efficiency of hESC-RPE to rescue photoreceptor degeneration in RCS rats.

Methods : A total of 91 immunosuppressed RCS rats were enrolled. On postnatal day (P) 21, 70 rats received hESC-RPE cells at doses of 30 000, 60 000, or 120 000 cells/eye, while 21 rats were injected with vehicle. Retinal function was evaluated using optokinetic response (OKR) and electroretinography (ERG) on Days 30, 60 and 90 post-transplantation; optical coherence tomography and color fundus were performed on Days 1, 30, 60 and 90. Eyes were collected for immunohistochemistry.

Results : Eyes that received hESC-RPE cells showed a significant slowdown on the progression of photoreceptor degeneration compared to control eyes. Photoreceptor rescue (thickness of the ONL) was most prominent at Day 30. Retinal autofluorescence resulting from the debris of dead photoreceptors was decreased in cell-injected eyes compared to control at Day 30. hESC-RPE cell doses were associated with greater scotopic b-wave amplitudes compared to control at Day 30, suggesting that RPE cells effectively slowdown degeneration in RCS rats. At Day 90, b wave amplitudes were sharply reduced, suggesting severe retinal degeneration resembling the phenotype of retinitis pigmentosa. Visual acuity decreased progressively, but higher OKR gains compared to control eyes were observed for RPE cells treated eyes on Days 30 and 90. Ku80-positive cells were present in all the eyes that received hESC-RPE cells, regardless of dose, often found integrated into the host RPE where they were co-stained with Bestrophin 1. Ki67-positive cells were rare and when present, co-stained with Ku80 in cells that are not integrated into the host RPE. Oct-4/Ku80-positive cells were rarely identified.

Conclusions : Sub-retinal delivery of hESC-RPE cells has effectively slowdown photoreceptor degeneration in RCS rats as evidenced by enhanced ERG parameters and higher OKR gains. The low cell dose was less efficacious compared to mid and high doses. These findings suggest that treatment with RPE cells ameliorates photoreceptor degeneration in RCS rats.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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