RiboTag-based profiling of actively translating transcripts in Nrf2-deficient and wildtype Müller cells in a mouse model of oxygen-induced retinopathy

Müller cells play a critical role in retinal angiogenesis and inflammation, particularly in ischemic retinopathies such as oxygen-induced retinopathy (OIR). Here, we employed actively translating transcriptome profiling using RiboTag technology to selectively examine gene expression in Müller cells with and without Nrf2, a master regulator of oxidative stress responses, during OIR. Conditional deletion of Nrf2 in Müller cells exacerbated retinal avascular areas and pathological neovascularization in the OIR model, without altering Müller cell number or viability. RiboTag-based RNA sequencing and pathway analysis identified dysregulation of oxidative phosphorylation and acute phase signaling, along with suppression of pathways related to neuronal signaling. Müller cell Nrf2 deficiency resulted in dysregulation of multiple genes involved in acute-phase response, inflammation, and angiogenesis. These findings uncover a critical role for Nrf2 in maintaining Müller cell homeostasis and identify molecular signatures by which its loss amplifies retinal gliosis and pathological angiogenesis.