Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (1): 406-416.doi: 10.4103/NRR.NRR-D-23-01741

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Contribution of ferroptosis and SLC7A11 to lightinduced photoreceptor degeneration

Xiaoxu Huang1, 2, #, Yumeng Zhang1, 2, #, Yuxin Jiang1, 2, #, Tong Li1, 2, Shiqi Yang1, 2, Yimin Wang1, 2, Bo Yu1, 2, Minwen Zhou1, 2, Guanran Zhang1, 2, Xiaohuan Zhao1, 2, *, Junran Sun1, 2, *, Xiaodong Sun1, 2   

  1. 1 Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China;  2 National Clinical Research Center for Eye Diseases; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
  • Online:2026-01-15 Published:2025-04-24
  • Contact: Junran Sun, MD, emiliesun@sina.com; Xiaohuan Zhao, MD, zhaoxiaohuanleslie@163.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82171076 (to XS) and U22A20311 (to XS), 82101168 (to TL); Shanghai Science and technology Innovation Action Plan, No. 23Y11901300 (to JS); Science and Technology Commission of Shanghai Municipality, No. 21ZR1451500 (to TL); and Shanghai Pujiang Program, No. 22PJ1412200 (to BY).

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Abstract: Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss. Ferroptosis has been demonstrated to be associated with retinal degenerative diseases. However, the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored. Bioinformatics and biochemical analyses in this study revealed xC– , solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model. This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway, through which cystine depletion, iron ion accumulation, and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment. We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo. Conversely, solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H2O2-induced ferroptosis of 661W cells. These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.

Key words: age-related macular degeneration, ferroptosis, light exposure damage, oxidative stress, pathway, photoreceptor, programmed cell death, solute carrier family 7 member 11 (SLC7A11)