June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Single-cell analysis reveals a compensatory role of Muller glia in a mouse retinitis pigmentosa model
Author Affiliations & Notes
  • Yohei Tomita
    Ophthalmology, Harvard Medical School, Boston Childre's Hospital, Boston, Massachusetts, United States
  • Chenxi Qiu
    Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
  • Edward Bull
    Ophthalmology, Harvard Medical School, Boston Childre's Hospital, Boston, Massachusetts, United States
  • William Allen
    Ophthalmology, Harvard Medical School, Boston Childre's Hospital, Boston, Massachusetts, United States
  • Yumi Kotoda
    Ophthalmology, Harvard Medical School, Boston Childre's Hospital, Boston, Massachusetts, United States
  • Zhongjie Fu
    Ophthalmology, Harvard Medical School, Boston Childre's Hospital, Boston, Massachusetts, United States
    The Manton Center for Orphan Disease, Boston Children’s Hospital, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Yohei Tomita, None; Chenxi Qiu, None; Edward Bull, None; William Allen, None; Yumi Kotoda, None; Zhongjie Fu, None
  • Footnotes
    Support  Manpei Suzuki Diabetic Foundation, Alcon Research Institute, and Bert M. Glaser, MD Award for Innovative Research in Retina (YT), Boston Children's Hospital Manton Center for Orphan Disease Research, OFD/BTREC/CTREC Faculty Career Development Grant, and Ophthalmology Foundation, Little Giraffe Foundation, Mass Lions Eye Foundation (ZF);
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 458. doi:
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    • Get Citation

      Yohei Tomita, Chenxi Qiu, Edward Bull, William Allen, Yumi Kotoda, Zhongjie Fu; Single-cell analysis reveals a compensatory role of Muller glia in a mouse retinitis pigmentosa model. Invest. Ophthalmol. Vis. Sci. 2021;62(8):458.

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

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Abstract

Purpose : Retinitis pigmentosa (RP) is a set of >60 hereditary retinal diseases characterized by degeneration of rod, then cone photoreceptors. It is typically diagnosed in adolescence and patients lose vision during adulthood. Gene therapy has been approved for only one gene in RP and developing gene therapies for >60 genetic causes is time consuming and costly. Therefore, we investigated retinal cellular responses to photoreceptor abnormalities in a mouse RP model to find a potential generic target to treat RP.

Methods : Cellular responses in each major retinal cell type in RP model (P23H; mutation of rhodopsin) and wild-type mice were analyzed using single-cell transcriptomics. Morphological changes were examined in P23H and wild-type mice retinas with OCT and immunohistochemistry (IHC) staining.

Results : OCT analysis showed thinning of the outer nuclear layer (ONL) and IS/OS layer in P23H versus wild-type mice at one-month old (p<0.001). Genes involved in IS/OS segments, photoreceptor cell cilia, and photoreceptor development were significantly decreased in both rod and cone clusters, in line with the structural changes seen with immunohistochemistry. The genes involved in energy production and metabolic pathways associated with this loss were notably decreased in both rods and cones. Furthermore, in the Müller glia/astrocyte cluster, there was a remarkable up-regulation in pathways responsible for photoreceptor maintenance, which was decreased in rods and cones.

Conclusions : Enhancing photoreceptor metabolism and modulating Müller glial responses may potentially serve as a generic approach to protect against retinal degeneration in RP.

This is a 2021 ARVO Annual Meeting abstract.

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