Time-Resolved Oxidative Stress and Apoptosis in Murine Retina under Acute Hypobaric Hypoxia with Parallel Activation of the LIF-JAK-STAT3 Axis.

High-altitude retinopathy (HAR) arises under acute hypobaric hypoxia (AHH), yet the temporal coupling of oxidative stress, apoptosis and cytokine signaling in the retina remains unclear. We exposed healthy male C57BL/6 mice to a hypobaric chamber (≈5,000 m) for 2-72 h, with normoxic controls at 1,500 m (n = 3 eyes/group). Haematoxylin-eosin sections quantified total and laminar thickness; at 24 h, bulk RNA-seq profiled transcripts. Reactive oxygen species (ROS) were assayed by dihydroethidium, and Western blotting/immunofluorescence evaluated Bax, Bcl-2/Bcl-xL, cleaved caspase-3, cytochrome c, poly(ADP-ribose) polymerase-1, tumour necrosis factor-α, phosphorylated Janus kinase-1 (p-JAK1), phosphorylated signal transducer and activator of transcription-3 (p-STAT3), leukemia inhibitory factor (LIF) and LIF receptor (LIFR). Total retinal thickness increased from 173.10 ± 0.36 μm (control) to 227.99 ± 0.33 μm at 24 h and 234.61 ± 0.39 μm at 72 h, with concordant GCL/INL/ONL thickening. RNA-seq showed enrichment of hypoxia/oxidative-stress, apoptotic, and JAK-STAT pathways with Lif/Lifr up-regulation. ROS rose from 12 h and peaked at 72 h (p < 0.05). Pro-apoptotic indices (Bax/Bcl-2, Bax/Bcl-xL, cleaved caspase-3/total) and cytochrome c, PARP-1, and TNF-α increased with exposure. p-JAK1 rose from 12 to 72 h, whereas p-STAT3 peaked at 48 h and remained elevated at 72 h. LIF/LIFR protein accumulated from 2-72 h (48 h apex). These time-resolved data reveal progressive oedema with sustained oxidative burden and a LIF-JAK1-STAT3 activation peak, suggesting a therapeutic window in AHH-induced retinal injury.