Nuclear GAPDH: changing the fate of Müller cells in diabetes

Abstract

Müller cells, the primary glial cells are a crucial component of the retinal tissue performing a wide range of functions including maintaining the blood-retinal barrier. Several studies suggest that diabetes leads to Müller cell dysfunction and loss. The pathophysiology of hyperglycemia-induced cellular injury of Müller cells remains only poorly understood. Recently, the concept that translocation of the predominantly cytosolic glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to the nucleus and its accumulation in this cellular compartment alters transcriptional events associated with cell death induction has gained major interest. High glucose conditions induce nuclear translocation and accumulation of GAPDH in the nucleus of Müller cells in vivo and in vitro. With regards to Müller cell dysfunction, the effects of nuclear accumulation of GAPDH are multifaceted. Considering the functional versatility of GAPDH including gene regulation, DNA repair, telomere protection, etc., it is of immense importance to explore possible GAPDH actions to unravel the mysteries around the role of GAPDH in hyperglycemia-induced cellular changes in order to develop novel therapeutic strategies. Therefore, this review focuses on the molecular events associated with the nuclear translocation of GAPDH and how it affects the fate of Müller cells in diabetes.