June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Improving Regenerative by Co-transplanting Cone Photoreceptors and Retinal Pigmented Epithelium Cells
Author Affiliations & Notes
  • Kang Li
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Ying Liu
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Gregory Konar
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Minda McNally
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Yuchen Lu
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Zhuolin Li
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Mandeep S Singh
    Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Kang Li None; Ying Liu None; Gregory Konar None; Minda McNally None; Yuchen Lu None; Zhuolin Li None; Mandeep Singh Revision Therapeutics, Johnson & Johnson, Third Rock Ventures, Bayer Healthcare, Novartis Pharmaceuticals, W. L. Gore & Associates, Deerfield, Trinity Partners, Kala Pharmaceuticals, Acucela, and Ionis Pharmaceuticals, Code C (Consultant/Contractor), Bayer, Code F (Financial Support)
  • Footnotes
    Support  NIH grant RO1EY033103
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2733. doi:
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      Kang Li, Ying Liu, Gregory Konar, Minda McNally, Yuchen Lu, Zhuolin Li, Mandeep S Singh; Improving Regenerative by Co-transplanting Cone Photoreceptors and Retinal Pigmented Epithelium Cells. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2733.

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

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Abstract

Purpose : In nonexudative age-related macular degeneration (AMD) patients, cone photoreceptor degeneration is typically the ultimate cause of vision loss that occurs in the center of the visual field. Transplanting exogenous cone cells is a potential treatment to restore visual function for these patients. However, preclinical studies on cone transplantation have generally shown poor donor cone survival following transplantation, thus posing a major barrier to clinical translation. It is well known that cones normally depend on retinal pigment epithelium (RPE) cells for homeostasis and function. Therefore, we aimed to study co-transplantation of cones and RPE to leverage donor RPE support to maximize donor cone survival following transplantation.

Methods : We first collected the neural retina cells and RPE cells from our reported cone-rich and -labeled donor mouse model OPN1LW-EGFP/NRL−/− mice (P3-P6). Then we co-transplanted the cones and RPE cells into the Rd1-NOD/SCID-albino recipient mice that exhibit retinal degeneration, immunodeficiency, and non-pigmented RPE. The control groups included a cone-only transplant group and a PBS transplant group (N=10 per group). Over three months following transplantation, we assayed graft survival generally, and cone survival specifically, by optical coherence tomography (OCT) and immunohistochemistry against cone-specific antigens.

Results : By OCT imaging at 1, 2, and 3 months after transplantation, we observed that the surviving grafts in the cone and RPE co-transplant group were significantly larger than those in the cone-only transplant group. We also analyzed the abundance of green fluorescent protein (GFP)+ donor cone survival and found greater GFP expression in the cone and RPE co-transplant group compared to controls. By computational nearest neighbor analysis, we noticed greater OPN1LW-EGFP and L/M-opsin expression in the transplanted donor cones that were in proximity with the transplanted RPE compared to more distantly located cone cells (p<0.05).

Conclusions : Cone photoreceptor and RPE co-transplantation may improve donor cone photoreceptor survival and maturation following transplantation, although the specific mechanisms underlying improved survival versus maturation require further study. The co-transplantation strategy could potentially be used as a future treatment strategy for late dry AMD.

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

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