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Introduction The hypothalamic–pituitary–adrenal (HPA) axis is a critical neuroendocrine system that maintains homeostasis, particularly through its response to stress and its modulation of the immune system ( With aging, the HPA axis plays a pivotal role in stress response and immunomodulation ( Stress, defined as perceived threat to homeostasis, involves key components located in the hypothalamus (paraventricular nucleus), anterior pituitary gland, and adrenal glands, collectively forming the HPA axis ( Oxidative stress is associated with redox reactions involving hemoglobin (Hb), nitrite, and nitric oxide (NO), leading to the formation of highly toxic peroxynitrite when NO reacts with superoxide released during Hb autoxidation ( The primary role of cellular γ-glutamyltranspeptidase (GGT) is to metabolize extracellular reduced glutathione (GSH), facilitating intracellular GSH synthesis

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RPEC hypertrophy occurs in mice with iron overload, resulting in impaired RPE function