June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Retinoschisin deficiency induces persistent aberrant waves of activity affecting neuroglial signaling in the developing retina
Author Affiliations & Notes
  • Cyril Eleftheriou
    Burke Neurological Institute, White Plains, New York, United States
  • Carlo Corona
    Burke Neurological Institute, White Plains, New York, United States
  • Shireen Khattak
    Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
  • Elena Ivanova
    Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
    Burke Neurological Institute, White Plains, New York, United States
  • Paola Bianchimano
    Mount Sinai Health System, New York, New York, United States
    Burke Neurological Institute, White Plains, New York, United States
  • Yang Liu
    Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
  • Duo Sun
    Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
  • Rupesh Singh
    Cleveland Clinic, Cleveland, Ohio, United States
  • Julia Batoki
    Cleveland Clinic, Cleveland, Ohio, United States
  • J Jason McAnany
    University of Illinois at Chicago, Chicago, Illinois, United States
  • Neal S Peachey
    Cleveland Clinic, Cleveland, Ohio, United States
    Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, United States
  • Carl Romano
    Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
  • Botir Sagdullaev
    Regeneron Pharmaceuticals Inc, Tarrytown, New York, United States
    Burke Neurological Institute, White Plains, New York, United States
  • Footnotes
    Commercial Relationships   Cyril Eleftheriou None; Carlo Corona None; Shireen Khattak Regeneron, Code E (Employment); Elena Ivanova Regeneron, Code E (Employment); Paola Bianchimano None; Yang Liu Regeneron, Code E (Employment); Duo Sun Regeneron, Code E (Employment); Rupesh Singh None; Julia Batoki None; J Jason McAnany None; Neal Peachey None; Carl Romano Regeneron, Code E (Employment); Botir Sagdullaev Regeneron, Code E (Employment)
  • Footnotes
    Support  R01 EY029796 & R01 EY026576
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2655. doi:
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    • Get Citation

      Cyril Eleftheriou, Carlo Corona, Shireen Khattak, Elena Ivanova, Paola Bianchimano, Yang Liu, Duo Sun, Rupesh Singh, Julia Batoki, J Jason McAnany, Neal S Peachey, Carl Romano, Botir Sagdullaev; Retinoschisin deficiency induces persistent aberrant waves of activity affecting neuroglial signaling in the developing retina. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2655.

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

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Abstract

Purpose : X-linked juvenile retinoschisis (XLRS) is an early onset inherited condition characterized by abnormal retinoschisin (RS1) expression, early visual deficiencies and cystic retinal lesions. We characterize a series of novel dysfunctions at the cellular level of the developing retina of mice lacking RS1.

Methods : We studied spontaneous intracellular calcium dynamics in male mice expressing GCaMP6f in neuronal, glial, and vascular cells and compared results from Rs1 knockouts (Rs1-/Y) and controls (Rs1+/Y). Optophysiological assessment was carried out in live wholemount retinal explants of cohorts aged P10-11, P14-15, P20-22, and P60-65. Additionally, we performed in vivo OCT imaging of retinal cysts and immunohistochemical characterization of retinoschisin expression in the retina.

Results : The development of retinal cysts imaged in vivo by OCT is paralleled by the appearance of aberrant spontaneous neuro-glial signals after postnatal day 13. These presented as glutamate-driven wavelets of neuronal and Müller glia activity spanning all retinal layers that disrupt light-induced signaling.

Conclusions : This study highlights the critical role that RS1 plays in early retinal development. Additionally, it confers a functional role to RS1 beyond the scope of an adhesion molecule and identifies a tight bracket for the onset of dysfunction, a potential temporal target for therapeutic intervention.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

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