Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies

Metal ions are indispensable for sustaining normal cellular functions and preserving tissue integrity, as they participate in enzymatic catalysis, signal transduction, and antioxidant defense. However, dysregulation of metal ion homeostasis, particularly during aging, disrupts cellular balance and significantly drives the development and progression of age-related ocular diseases, including age-related macular degeneration, glaucoma, diabetic retinopathy, and cataracts. Specifically, metal ions modulate key stress responses that are central to aging and ocular pathogenesis. Excessive accumulation of redox-active metals triggers the generation of reactive oxygen species that induce oxidative damage to lipids, proteins, and DNA. Meanwhile, deficiencies in essential metals, such as iron, zinc, copper, and calcium, impair antioxidant enzyme activity and disrupt DNA repair, exacerbating cellular dysfunction and senescence. The therapeutic potential of these metal chelators and antioxidants in restoring their balance, alleviating oxidative stress, and slowing the progression of age-related ocular diseases has been well documented. A deeper understanding of how metal ions influence these processes is crucial for developing more targeted and effective treatments. This article systematically reviews the roles of metal ions in age-related ocular diseases, with a focus on their effects on stress responses and potential therapeutic strategies.