Abstract: Homeostatic regulation of the internal environment is an important characteristic of natural ecosystems to maintain dynamic stability. Abnormal regulation of ion homeostasis in the body causes abnormal protein synthesis and folding in retinal cells, leading to the formation of various degenerative retinal diseases, including retinitis pigmentosa. Abnormalities in metal ion homeostasis include the “iron death” of elevated lipid peroxides and reactive oxygen species and reduced glutathione and glutathione peroxidase 4 levels due to iron overload; abnormal cytoplasmic and mitochondrial aggregation of calcium that precedes apoptosis; and the decrease of endogenous zinc ions in the retinal pigment epithelium with age, but the increase of extracellular aggregation all suggest a possible relationship between the abnormal homeostasis of metal ions and the formation of retinal degenerative disease. A number of novel interventions and technologies have shown promising therapeutic potential to address these mechanisms, including iron chelators such as “deferiprone”, zinc-desferrioxamine, and gene therapy for iron death, new calcium channel blockers such as D-cis-diltiazem and nivadipine, and the oral administration of zinc sulfate or zinc-monocysteine compound to restore zinc homeostasis. These strategies provide new ideas for intervening in retinal degenerative diseases, providing strong support for the important role of metal ion homeostatic regulation in disease treatment. (Int Rev Ophthalmol, 2024, 48:  471-475)

Key words: metal ion homeostasis, retinal degenerative disease