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YAP Regulates the Nrf2 Signaling Axis to Attenuate Oxidative Stress and Neuroinflammation in Retinal Ganglion Cell

Shirui Zhou1, Fumin Yang2, Ke Ding1

  • 1Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Investigative Ophthalmology & Visual Science
|July 10, 2026
PubMed
Abstract

Insights

Activating Yes-associated protein (YAP) protected retinal ganglion cells (RGCs) from injury by reducing oxidative stress and neuroinflammation. This highlights YAP

Area of Science:

  • Neuroscience
  • Cell Biology
  • Ophthalmology

Background:

  • Oxidative stress is a primary cause of retinal ganglion cell (RGC) degeneration following optic nerve injury.
  • The Hippo pathway effector Yes-associated protein (YAP) influences cellular stress responses, but its role in RGC oxidative stress is not well understood.

Purpose of the Study:

  • To investigate the role of YAP in protecting RGCs against injury-induced oxidative stress and degeneration.
  • To explore the mechanistic link between YAP activation, antioxidant pathways (Nrf2), and neuroinflammation in RGCs.

Main Methods:

  • Utilized an in vivo optic nerve crush (ONC) model and an in vitro oxidative stress model with primary RGCs.
  • Modulated YAP expression pharmacologically and genetically.
  • Assessed effects on Nrf2 signaling, oxidative stress markers (ROS, SOD-1/2, Nqo-1), and neuroinflammation (microglial and astrocytic activation) using qPCR and immunofluorescence.

Main Results:

  • YAP activation significantly enhanced RGC survival in both in vivo and in vitro models, while YAP suppression worsened degeneration.
  • Activated YAP correlated with increased Nrf2 signaling, elevated antioxidant enzyme expression (Nqo-1, SOD-2), and reduced reactive oxygen species (ROS).
  • YAP activation attenuated neuroinflammation by decreasing microglial and astrocytic activation, effects reversed by YAP inhibition.

Conclusions:

  • YAP acts as a significant neuroprotective factor in RGC injury models.
  • YAP activation mitigates oxidative stress and neuroinflammation, mechanistically linked to Nrf2-mediated antioxidant pathways.
  • The interaction between YAP and Nrf2 presents a potential therapeutic target for RGC injury.

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