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This study used the sodium iodate (SI, a chemical oxidant)\u2010induced animal dry AMD model to investigate the 6dS\u2010mediated antioxidant mechanism. 6dS reduced SI\u2010induced cytotoxicity, including ferrous iron accumulation, lipid peroxidation, glutathione (GSH) depletion, and ferroptosis in ARPE\u201019 cells. SI injection in rats induced cell death and lipid peroxidation in the RPE layer, along with retinal atrophy and electrophysiological dysfunction, recapitulating features of dry AMD that were counteracted by 6dS eye drop treatment. Mechanistically, 6dS induced the expression of SLC7A11 (solute carrier family seven member 11) and glutathione peroxidase 4 (GPX4) to alleviate SI\u2010induced GSH depletion and lipid peroxidation. Inhibitors targeting the PEDF receptor, SLC7A11, and GPX4 abolished the 6dS effect. Our study proposes an antioxidant mechanism through which PEDF receptor signalling links to the SLC7A11\/GSH\/GPX4 axis to alleviate intracellular redox imbalance. These findings suggest that 6dS eye drops may be a promising treatment for dry AMD.<\/jats:p>","DOI":"10.1111\/jcmm.70693","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T08:39:32Z","timestamp":1753346372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A <scp>PEDF<\/scp>\u2010Derived Short Peptide Prevents Sodium Iodate\u2010Induced Retinal Degeneration in Rats by Activating the <scp>SLC7A11<\/scp>\/<scp>GSH<\/scp>\/<scp>GPX4<\/scp> Pathway in the <scp>RPE<\/scp> Cells"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4318-3439","authenticated-orcid":false,"given":"Tsung\u2010Chuan","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Medical Research Mackay Memorial Hospital  New Taipei City 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