Crosstalk between estrogen signaling and Fas-mediated apoptosis determines neuronal resilience after menopause.

Here, we investigated how mimicking age-related endocrine decline influences the susceptibility of retinal neurons to ischemic stress and whether simultaneous targeting of survival and apoptotic pathways restores neuronal resilience.

Pharmacological modulation revealed that selective estrogen receptor signaling or Fas pathway inhibition alone provided partial neuroprotection.

Ex vivo retinal explants (N = 15) confirmed that dual pathway modulation drives a 2-fold increase in neuronal survival and significantly limits cytotoxicity, supporting a direct cellular mechanism.