Metformin Attenuates RGC Injury by Blocking the HIF-1α-VEGF Pathway in A Mouse Model of Retinal Ischemia-Reperfusion Injury

Wenjuan Yang, Pengfei Ma, Xing Guo, Cuiyin Zhang, Nixian Yu

Article ID: 7793
Vol 38, Issue 1, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243801.64
Received: 20 January 2024; Accepted: 20 January 2024; Available online: 20 January 2024; Issue release: 20 January 2024

Abstract

Backgrounds and Objective: Retinal ischemia-reperfusion (I/R) injury is a main cause of retinal ganglion cell (RGC) damage, leading to visual impairment. In this study, we investigated the therapeutic potential of metformin, an antidiabetic drug, in alleviating RGC injury in a mouse model of retinal I/R injury. We aimed to explore the role of metformin in modulating the hypoxia inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) pathway, which is known to be involved in the development of retinal ischemia. Methods: Eight-week-old male C57BL/6 J mice (6 each group), anesthetized with pentobarbital, were treated with the intraperitoneal injection of metformin in the model + metformin group after one day by a retinal I/R procedure. Three days after the I/R injury, the therapeutic effect was evaluated by the staining of surviving RGCs, real-time quantitative PCR (qRT-PCR), and Western blot analysis. Results: Our findings revealed that metformin treatment reduced RGC loss in retinal I/R injury model. Mechanistically, metformin administration effectively inhibited HIF-1α and vascular endothelial growth factor (VEGF), which are key components of the HIF-1α-VEGF pathway, and were upregulated (p < 0.01) in the I/R injury group. Furthermore, metformin treatment resulted in the restoration of visual proteins, including opsin and rhodopsin, as well as the upregulation of neurotrophic factors (nerve growth factor (NGF) and Brain Derived Neurotrophic Factor (BDNF)) (p < 0.01), which play crucial roles in RGC survival and function. These results highlight the neuroprotective effects of metformin in attenuating RGC injury by suppressing the HIF-1α-VEGF pathway in a mouse model of retinal I/R injury. Conclusion: The findings suggest that metformin may be a potential therapeutic agent for the treatment of retinal ischemic disorders. Further investigations are needed to elucidate the underlying molecular mechanisms and validate the translational potential of metformin in clinical settings.


Keywords

metformin;retinal ischemia-reperfusion injury;HIF-1α;VEGF pathway;pyroptosis


References

Supporting Agencies



Copyright (c) 2024 Wenjuan Yang, Pengfei Ma, Xing Guo, Cuiyin Zhang, Nixian Yu




This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).