SOX2 haploinsufficiency promotes impaired vision at advanced age

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 (Sox2GFP) 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 Sox2GFP. 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.

Features of Retinal Neurogenesis as a Key Factor of Age-Related Neurodegeneration: Myth or Reality?

“…Moreover, a decline in Sox2 expression with age is seen in Müller cells and amacrine and ganglion neurons, and this decrease impairs the activity of these cells [117]. In that study, investigators found that aged Sox2GFP mice possess impaired visual function, indicating the critical role that Sox2 plays in age-related vision maintenance [117]. Astrocytic loss of Sox2 affects vascular architecture during maturity [119].…”

“…Loss of SOX2 forces Müller cells to aberrantly divide into a pair of postmitotic daughter cells, thereby causing Müllerglial-cell depletion and retinal degeneration [118]. Moreover, a decline in Sox2 expression with age is seen in Müller cells and amacrine and ganglion neurons, and this decrease impairs the activity of these cells [117]. In that study, investigators found that aged Sox2GFP mice possess impaired visual function, indicating the critical role that Sox2 plays in age-related vision maintenance [117].…”

“…This disorganization is concurrent with a thinning of the neural retina and an impairment of neuronal processes in the IPL and OPL. Moreover, there is a decrease in the b-wave amplitude in both young Sox2 mutant mice and aged Sox2GFP mice; therefore, retina function is affected negatively [116,117]. SOX2 plays an essential role in the maintenance of structural organization of the postnatal retina and in the quiescence of nascent Müller cells.…”

Features of Retinal Neurogenesis as a Key Factor of Age-Related Neurodegeneration: Myth or Reality?

“…This disorganization is concurrent with neural retina thinning and an impairment of neuronal processes in the IPL and the OPL. Moreover, there is a decrease in the b-wave amplitude in both young Sox2 mutant mice and aged Sox2GFP mice; therefore, the retina function is affected negatively [ 114 , 115 ]. SOX2 plays an essential role in the maintenance of the structural organization of the postnatal retina and in the quiescence of nascent Müller cells.…”

“…Loss of SOX2 forces Müller cells to aberrantly divide into a pair of postmitotic daughter cells, thereby causing Müller glial cell depletion and retinal degeneration [ 116 ]. Moreover, a decline in Sox2 expression with age is seen in Müller cells and in amacrine and ganglion neurons, and this decrease impairs the activity of these cells [ 115 ]. In that study, investigators found that aged Sox2GFP mice feature an impaired visual function, indicating the critical role that Sox2 plays in age-related vision maintenance [ 115 ].…”