铁死亡在玻璃体积血致视网膜损伤中的潜在作用：机制假说与干预前景

唐晶晶 赵靖 马文豪^{（通讯作者）}

右江民族医学院，广西百色，533000；

摘要：玻璃体积血（Vitreous Hemorrhage, VH）是多种眼病的严重并发症，红细胞溶解释放的血红素与游离铁介导的视网膜毒性是影响预后的关键因素。铁死亡是铁依赖的脂质过氧化调节性细胞死亡。本文基于其核心机制与视网膜铁稳态研究证据，提出积血后游离铁跨屏障蓄积、诱发视网膜神经元及光感受器铁死亡的假说，并综述铁螯合剂、NRF2激活剂与脂质过氧化抑制剂等干预策略。然而，目前仍缺乏积血模型直接证据，未来需动物模型等深入研究验证其因果作用，并评估早期清除积血与靶向干预的价值。

关键词：玻璃体积血；铁死亡；视网膜损伤；铁代谢；脂质过氧化

参考文献

[1]SHAIKH N, SRISHTI R, KHANUM A, et al. Vitreous hemorrhage: causes, diagnosis, and management[J]. Indian J Ophthalmol, 2023, 71(1): 28-38.

[2]PICARD E, DARUICH A, YOUALE J, et al. From rust to quantum biology: the role of iron in retina physiopathology[J]. Cells, 2020, 9(3): 705.

[3]SHU W, BAUMANN B H, SONG Y, et al. Ferrous but not ferric iron sulfate kills photoreceptors and induces photoreceptor-dependent RPE autofluorescence[J]. Redox Biol, 2020, 34: 101469.

[4]DIXON S J, LEMBERG K M, LAMPRECHT M R, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072.

[5]STOCKWELL B R, FRIEDMANN ANGELI J P, BAYIR H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease[J]. Cell, 2017, 171(2): 273-285.

[6]BERSUKER K, HENDRICKS J M, LI Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis[J]. Nature, 2019, 575(7784): 688-692.

[7]GNANA-PRAKASAM J P, MARTIN P M, SMITH S B, et al. Expression and function of iron-regulatory proteins in retina[J]. IUBMB Life, 2010, 62(5): 363-370.

[8]DARUICH A, LE ROUZIC Q, JONET L, et al. Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection[J]. Sci Adv, 2019, 5(1): eaau9940.

[9]CHHATWAL S, ANTONY H, LAMEI S, et al. A systematic review of the cell death mechanisms in retinal pigment epithelium cells and photoreceptors after subretinal hemorrhage: implications for treatment options[J]. Biomed Pharmacother, 2023, 167: 115572.

[10]ZHAO T, GUO X, SUN Y. Iron accumulation and lipid peroxidation in the aging retina: implication of ferroptosis in age-related macular degeneration[J]. Aging Dis, 2021, 12(2): 529-551.

[11]FAN X, XU M, REN Q, et al. Downregulation of fatty acid binding protein 4 alleviates lipid peroxidation and oxidative stress in diabetic retinopathy by regulating peroxisome proliferator-activated receptor γ-mediated ferroptosis[J]. Bioengineered, 2022, 13(4): 10540-10551.

[12]YE M, JIANG Y, GONG H, et al. Resveratrol alleviated diabetic retinal neuronal ferroptosis induced by high glucose through inhibiting HIF-1α and HMOX1 pathway[J]. Exp Eye Res, 2026, 265: 110872.

[13]YAO F, PENG J, ZHANG E, et al. Pathologically high intraocular pressure disturbs normal iron homeostasis and leads to retinal ganglion cell ferroptosis in glaucoma[J]. Cell Death Differ, 2023, 30(1): 69-81.

[14]QIN Q, YU N, GU Y, et al. Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury[J]. Cell Death Dis, 2022, 13(5): 507.

[15]SHAHANDEH A, BUI B V, FINKELSTEIN D I, et al. Effects of excess iron on the retina: insights from clinical cases and animal models of iron disorders[J]. Front Neurosci, 2021, 15: 794809.

[16]LI Y, CHENG Z X, LUO T, et al. Therapeutic potential of iron chelators in retinal vascular diseases[J]. Int J Ophthalmol, 2023, 16(11): 1899-1910.

[17]FRIEDMANN ANGELI J P, SCHNEIDER M, PRONETH B, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice[J]. Nat Cell Biol, 2014, 16(12): 1180-1191.