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Introduction: Alkali burn injury of the cornea can lead to severe vision loss and blindness. One of the main contributors to this outcome is the development of angiogenesis, or the growth of new blood vessels in the cornea. This study investigated the role of reactive oxygen species (ROS) in the development of angiogenesis after alkali burn injury, and the effects of antioxidants in preventing this process.
Methods: The corneal epithelia of SOD-1-deficient mice or wild-type (WT) mice were removed after application of 0.15 N NaOH to establish the animal model of alkali burn. ROS production was semiquantitatively measured by dihydroethidium (DHE) fluorescence. Angiogenesis was visualized by CD31 immunohistochemistry. The effects of the specific NF-κB inhibitor DHMEQ, the antioxidant N-acetyl-L-cysteine (NAC), and hydrogen (H2) solution were observed.
Results: The study found that ROS production in the cornea was significantly enhanced immediately after alkali injury, as shown by increased DHE fluorescence (P<0.01). This was associated with a significant increase in the activation of the NF-κB pathway and the upregulation of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1), leading to a significantly larger area of angiogenesis. Angiogenesis in SOD-1-/- mice corneas were significantly higher in WT mice (P<0.01), confirming the role of ROS. Pretreatment with the specific NF-κB inhibitor DHMEQ or the antioxidant NAC significantly reduced corneal angiogenesis by downregulating the NF-κB pathway (P<0.01) in both WT and SOD-1-/- mice. Furthermore, the study showed that irrigation of the cornea with hydrogen (H2) solution significantly reduced angiogenesis after alkali-burn injury (P<0.01).
Conclusion: The results of this study suggest that immediate antioxidant therapy with H2-enriched irrigation solution is a new potent treatment for preventing angiogenesis in cornea after alkali burn injury. The study also highlights the role of ROS in the development of angiogenesis and the potential for antioxidants to prevent this process. It is important to note that further studies are necessary to determine the underlying mechanisms of these protective effects and to investigate the potential for hydrogen therapy to be used in human patients. Additionally, it is worth noting that hydrogen water or molecular hydrogen water are not the same as H2 solution used in this study and further research is needed to investigate their effects.
Kubota, M., et al., Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model. Investigative Ophthalmology and Visual Science, 2011. 52(1): p. 427-33.