June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
A traceable and functional cone-rich donor for allogenic photoreceptor transplantation in mouse models of degenerative retinal diseases
Ying Liu; Derek Teng; Gregory Konar; Dzhalal Agakishiev; Alexis Biggs-Garcia; Sarah Harris-Bookman; Minda McNally; Catalina Garzon; Saalini Sastry; Mandeep Singh
Author Affiliations & Notes
  • Ying Liu
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Derek Teng
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Gregory Konar
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Dzhalal Agakishiev
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Alexis Biggs-Garcia
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Sarah Harris-Bookman
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Minda McNally
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Catalina Garzon
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Saalini Sastry
    Johns Hopkins University Zanvyl Krieger School of Arts and Sciences, Baltimore, Maryland, United States
  • Mandeep Singh
    Retina, Johns Hopkins Medicine Wilmer Eye Institute, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Ying Liu, None; Derek Teng, None; Gregory Konar, None; Dzhalal Agakishiev, None; Alexis Biggs-Garcia, None; Sarah Harris-Bookman, None; Minda McNally, None; Catalina Garzon, None; Saalini Sastry, None; Mandeep Singh, None
  • Footnotes
    Support  This work was supported by the Foundation Fighting Blindness (Career Development Award to MSS), The Shulsky Foundation, the Juliette RP Vision Foundation, Research to Prevent Blindness (unrestricted grant to the Wilmer Eye Institute), and the National Eye Institute Core Grant EY001765.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3286. doi:
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      Ying Liu, Derek Teng, Gregory Konar, Dzhalal Agakishiev, Alexis Biggs-Garcia, Sarah Harris-Bookman, Minda McNally, Catalina Garzon, Saalini Sastry, Mandeep Singh; A traceable and functional cone-rich donor for allogenic photoreceptor transplantation in mouse models of degenerative retinal diseases. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3286.

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Abstract

Purpose : Cone photoreceptor transplantation is a potential treatment for macular diseases. The optimal conditions for cone transplantation are poorly understood, partly because of the scarcity of cones in donor mice. To facilitate allogeneic cone photoreceptor transplantation studies in rodents, we aimed to create and characterize a donor mouse model containing a cone-rich retina with a cone-specific enhanced green fluorescent protein (EGFP) reporter.

Methods : We generated OPN1LW-EGFP/NRL-/- mice by crossing NRL-/- and OPN1LW-EGFP mice. We characterized the anatomical phenotype of OPN1LW-EGFP/NRL-/- mice using multimodal confocal scanning laser ophthalmoscopy (cSLO) imaging, immunohistology, and transmission electron microscopy. We evaluated retinal function using electroretinogram (ERG), including 465 and 525 nm chromatic stimuli. Retinal sheets from OPN1LW-EGFP/NRL-/- mice were transplanted subretinally into immunodeficient Rd1 mice.

Results : OPN1LW-EGFP/NRL-/- retinas were enriched with S-opsin+ cone photoreceptors in a dorsal-ventral distribution gradient. EGFP reporter expression occurred in L/M- and S-opsin expressing cells. Rosettes formed preferentially in the ventral retina. The outer retina in P35 OPN1LW-EGFP/NRL-/- was thinner than NRL-/- controls. The OPN1LW-EGFP/NRL-/- ERG response amplitudes to 465 nm stimulation were similar to, but to 535 nm stimulation were lower than, NRL-/- controls. Three months after transplantation, there were more S-opsin+ than L/M-opsin+ outer segments detected in recipients.

Conclusions : OPN1LW-EGFP/NRL-/- retinae were enriched with S-opsin+ cells. Sustained expression of EGFP facilitated the longitudinally tracking of donor cells. Transplanted cone-rich retinal sheet from OPN1LW-EGFP/NRL-/- mice survived and matured into subtype of cone photoreceptors. This novel cone-rich reporter mouse model is a useful tool for the study of cone photoreceptor transplantation as a treatment for macular diseases.

This is a 2021 ARVO Annual Meeting abstract.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Copyright © 2024 Association for Research in Vision and Ophthalmology.
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