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Ferroptosis: mechanisms and advances in ocular diseases

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Abstract

As an essential trace element in the body, iron is critical for the maintenance of organismal metabolism. Excessive iron facilitates reactive oxygen species generation and inflicts damage on cells and tissues. Ferroptosis, a newly identified iron-dependent type of programmed cell death, has been implicated in a broad set of metabolic disorders. Ferroptosis is mainly characterized by excess iron accumulation, elevated lipid peroxides and reactive oxygen species, and reduced levels of glutathione and glutathione peroxidase 4. The vast emerging literature on ferroptosis has shown that numerous diseases, such as cancers, neurodegeneration, and autoimmune diseases, are associated with ferroptosis. Meanwhile, recent studies have confirmed the relationship between ferroptosis and eye diseases including keratopathy, cataract, glaucoma, retinal ischemia-reperfusion injury, age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and retinoblastoma, indicating the critical role of ferroptosis in ocular diseases. In this article, we introduce the primary signaling pathways of ferroptosis and review current advances in research on ocular diseases involving iron overload and ferroptosis. Furthermore, several unanswered questions in the area are raised. Addressing these unanswered questions promises to provide new insights into preventing, controlling, and treating not only ocular diseases but also a variety of other diseases in the near future.

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Abbreviations

ROS:

Reactive oxygen species

Fer-1:

Ferrostatin-1

PUFA:

Polyunsaturated fatty acid

PUFA-PL:

Polyunsaturated fatty acid-containing phospholipid

ACSL4:

Acyl‑CoA synthetase long‑chain family member 4

GPX4:

Glutathione peroxidase 4

RTA:

Radical-trapping antioxidant

Fe3+ :

Ferric

Fe2+:

Ferrous

LIP:

Labile iron pool

FT:

Ferritin heavy chain

FTL:

Ferritin light chain

FPN:

Ferroportin

NCOA4:

Nuclear receptor coactivator 4

GSH  Glutathione           PLOOH:

Phospholipid hydroperoxide

LOX:

Lipoxygenase

FSP1:

Ferroptosis suppressor protein 1

SLC7A11:

Solute carrier family 7 member 11

BH4:

Tetrahydrobiopterin

DHODH:

Dihydroorotate dehydrogenase

NRF2:

Nuclear factor E2-related factor 2

CEC:

Corneal epithelial cell

HTP:

Heated tobacco product

CSE:

Cigarette smoke extract

DFO:

Deferoxamine

ARC:

Age-related cataract

LEC:

Lens epithelial cell

RGC:

Retinal ganglion cell

POAG:

Primary open-angle glaucoma

IVT:

Intravitreal

RIRI:

Retinal ischemia–reperfusion injury

AMD:

Age related macular degeneration

tBH:

Tert-butyl hydroperoxide

STGD:

Stargardt disease

atRAL:

All-trans-retinal

FAC:

Ferric ammonium citrate

LAMP 2:

Lysosomal membrane-associated 2 protein

RP:

Retinitis pigmentosa

SOD1:

Superoxide dismutase 1

DR:

Diabetic retinopathy

RB:

Retinoblastoma

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  1. Feng Wang and Ying Su have contributed equally to this work and worked as co-correspondence author.

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  1. Department of Ophthalmology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China

    Kexin Liu, Huazhang Li & Feng Wang

  2. Eye Hospital, The First Affiliated Hospital, Harbin Medical University, Harbin, China

    Ying Su

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Liu, K., Li, H., Wang, F. et al. Ferroptosis: mechanisms and advances in ocular diseases. Mol Cell Biochem 478, 2081–2095 (2023). https://doi.org/10.1007/s11010-022-04644-5

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