Int J Surg. 2025 Dec 4. doi: 10.1097/JS9.0000000000004146. Online ahead of print.
ABSTRACT
BACKGROUND: Glaucoma is an irreversible blinding eye disease characterized by the progressive loss of retinal ganglion cells (RGCs). In addition to the conventional visual pathways, RGCs can also mediate emotional responses through non-image forming visual pathways. Emerging evidence indicates that oxidative stress and mitochondrial dysfunction play pivotal roles in the pathogenesis of glaucoma. We found that a small-molecule compound extracted from celery seeds can regulate mitochondrial function and exert neuroprotective effects in glaucoma-related pathological damage.
MATERIALS AND METHODS: The protective effect of 3-n-Butylphthalide (NBP) on retinal ganglion cells was investigated using acute and chronic ischemia-reperfusion in vivo and in vitro models. Subsequently, transcriptome sequencing, targeted metabolomics, western blot, RT-qPCR, electrophysiology, and immunofluorescence were employed to further elucidate the potential molecular mechanisms through which NBP exerts neuroprotective effects by modulating mitochondrial function.
RESULTS: The results demonstrated that NBP significantly attenuated RGCs loss and improved retinal visual function following acute ocular hypertension (AOH) injury, indicating robust neuroprotective effects. Mechanistically, NBP improved mitochondrial morphology and function in retinal tissues and cultured cells, promoted mitochondrial energy metabolism, and activated mitophagy, potentially through modulation of the 5-HT2A/Maoa signaling axis, thereby reducing oxidative stress and apoptosis. Notably, we also observed that mice subjected to AOH exhibited depression- and anxiety-like behaviors, accompanied by increased Maoa expression and decreased 5-HT levels in the prefrontal cortex and hippocampus. NBP treatment effectively alleviated these behavioral and molecular abnormalities.
CONCLUSION: These findings offer new insights into the pathophysiological mechanisms of glaucoma and highlight NBP as a promising candidate for neuroprotection and mood regulation via the eye-brain axis, potentially informing future clinical strategies.
PMID:41342379 | DOI:10.1097/JS9.0000000000004146