SOX2 haploinsufficiency promotes impaired vision at advanced age

Leire Moreno-Cugnon; Ander Anasagasti; Maitane Ezquerra-Inchausti; Ander Izeta; Pedro de la Villa; Javier Ruiz-Ederra; Ander Matheu

doi:10.18632/oncotarget.26393

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Research Papers:

SOX2 haploinsufficiency promotes impaired vision at advanced age

Leire Moreno-Cugnon _, Ander Anasagasti, Maitane Ezquerra-Inchausti, Ander Izeta, Pedro de la Villa, Javier Ruiz-Ederra and Ander Matheu

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Oncotarget. 2018; 9:36684-36692. https://doi.org/10.18632/oncotarget.26393

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Abstract

Leire Moreno-Cugnon1, Ander Anasagasti2, Maitane Ezquerra-Inchausti2, Ander Izeta3, Pedro de la Villa4,5, Javier Ruiz-Ederra2,5 and Ander Matheu1,6

1Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastián, Spain

2Sensorial Neurodegeneration Group, Biodonostia Health Research Institute, San Sebastián, Spain

3Tissue Engineering Laboratory, Biodonostia Health Research Institute, San Sebastián, Spain

4Visual Neurophysiology, IRYCIS, University of Alcala, Madrid, Spain

5RETICS OFTARED, Madrid, Spain

6IKERBASQUE, Basque Foundation for Science and CIBERfes, Bilbao, Spain

Correspondence to:

Ander Matheu, email: [email protected]

Javier Ruiz-Ederra, email: [email protected]

Keywords: Sox2; haploinsufficiency; aging; retina stem cell progenitors; vision loss

Received: July 18, 2018 Accepted: November 01, 2018 Published: November 30, 2018

ABSTRACT

Age-related vision loss has been associated with degeneration of the retina and decline in Müller glia cell activity. Sox2 is a critical transcription factor for the development and maintenance of the mammalian retina. Here we determined the role of Sox2 in retinal aging. We observed a decline in the number of Sox2-positive Müller, amacrine and ganglion cells with age. We also explored the impact of Sox2 haploinsufficiency (Sox2^GFP) on the activity of Müller glia cells and vision loss with age. Reduction of Sox2-positive cells promoted impaired Müller glia cell function at advanced age of Sox2^GFP. These findings correlated with a significant decline in electroretinographic response in Sox2 haploinsufficient mice. Together, these results indicate that Sox2 is required for the maintenance of the transmission of visual information from cones and rods, and suggest that decline in Sox2 expression is responsible for retinal cell aging and age-related vision loss.

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Research Papers:

SOX2 haploinsufficiency promotes impaired vision at advanced age

Abstract