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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)
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.
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.
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.
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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