YAP activation in Müller cells alleviates oxidative stress in the rat retina after intravitreal injection with methylglyoxal.

Methylglyoxal (MGO), a highly reactive dicarbonyl compound produced via the glycolytic pathway, plays a key role in the pathogenesis of various diabetic complications, such as diabetic retinopathy. Müller cells provide neurotrophic support and maintain retinal homeostasis, including the redox balance. This dysfunction leads to retinal disease. Yes-associated protein (YAP), a major downstream effector of the Hippo pathway, plays a crucial role in regulating cell survival. In this study, we investigated the roles of Müller cell YAP during MGO-induced retinal injury using normal rats intravitreally injected with MGO and a rat Müller cell line (rMC-1). Immunohistochemistry revealed that MGO injection increased the glial fibrillary acidic protein immunoreactivity in Müller cells. The alignment of Müller cell nuclei was disrupted in MGO-treated retinas. YAP increased and activated in Müller cells two days after MGO injection. This increase in YAP levels was independent of the Hippo pathway and partially attributed to the upregulation of YAP mRNA levels. YAP inhibition by verteporfin exacerbated MGO-induced cell damage and decreased Bcl-xL levels in rMC-1 cells. Intravitreal verteporfin injection also enhanced MGO-induced retinal oxidative stress. Overall, our findings suggest that YAP activation in Müller cells alleviates oxidative stress in the retina following MGO-induced retinal injury.