The DOI matches its Crossref record; 150 of the 153 references it cites were found in a registry or an index.
Iron homeostasis and toxicity in retinal degeneration
Open accessAbstract
Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls. Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron-induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Retinal iron levels increase with age [1322], iron is significantly implicated in AMD [1323-1329], and iron chelation may help to reverse the process [1330].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1328]
Citations
Cites
Oxygen toxicity, oxygen radicals, transition metals and disease
Halliwell, B., & Gutteridge, J. M. C. (1984) · Biochemical Journal · doi:10.1042/bj2190001 · Cited by 5,330
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166
Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168
The Role of Oxidative Stress in the Pathogenesis of Age-Related Macular Degeneration
Beatty, S., Koh, H.-H., Phil, M., Henson, D., & Boulton, M. (2000) · Survey of Ophthalmology · doi:10.1016/s0039-6257(00)00140-5 · Cited by 2,051
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697
Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422
Flagged first, then by citations
3 of the 153 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Knave, 1969, Electroretinography in eyes with retained intraocular metallic foreign bodies, Acta Ophthalmol., 100, 4
- Piga, 2002, Phase II study of oral chelator ICL670 in thalassemia patients with transfusional iron overload: efficacy, safety pharmacokinetics and pharmacokinetics and pharmacodynamics after 6 months of therapy [abstract], Blood, 100, 5a
Cited by
Sorted by citations
Items 201–261 of 261
Ocular biomarkers in diseases and toxicities
Kontadakis, G. A., Plaka, A. D., Fragou, D., Kymionis, G. D., & Tsatsakis, A. M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-404630-6.00019-1 · Cited by 4
Rajkumar, S., Vidya, N. G., Ankit, G. D., & Vasavada, A. R. (2018) · International Journal of Ophthalmology and Clinical Research · doi:10.23937/2378-346x/1410091 · Cited by 4
La dégénérescence maculaire liée à l’âge: La piste du fer
Courtois, Y., Youale, J., Béhar‐Cohen, F., & Picard, É. (2020) · médecine/sciences · doi:10.1051/medsci/2020096 · Cited by 4
Ateş, B., Trital, A., Jeyalatha, M. V., Xu, L., Kenlee, J., Nuran Ercal, A., & Yang, H. (2025) · Biomacromolecules · doi:10.1021/acs.biomac.5c01704 · Cited by 3
Eder, K., Langosz, P., Danikiewicz-Zagała, M., Leszczyński, R., & Wyględowska‐Promieńska, D. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27031336 · Cited by 3
Niksirat, H., Siino, V., Steinbach, C., & Levander, F. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e33057 · Cited by 3
Asleh, S. A., Lederman, M., Weinstein, O., Horowitz, S., Meir, T., Lahad, A., Goldstein, N., Sharon, D., Israel, S., & Chowers, I. (2009) · Ophthalmic Genetics · doi:10.3109/13816810903147998 · Cited by 3
Advanced nanomedicines for the treatment of age-related macular degeneration
Kwon, Y., & Han, Z. (2024) · Nanoscale · doi:10.1039/d4nr01917b · Cited by 3
Song, Q., Zhang, F., Han, X., Yang, Y., Zhao, Y., & Duan, J. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108642 · Cited by 3
Review of Emerging Treatments for Age-Related Macular Degeneration
Zarbin, M. A., & Rosenfeld, P. J. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-606-7_1 · Cited by 3
Retinal damages in turner workers of a factory exposed to intraocular foreign bodies
Shushtarian, S. M. S., Mirdehghan, M. S., & Valiollahi, P. (2008) · Indian Journal of Occupational and Environmental Medicine · doi:10.4103/0019-5278.44696 · Cited by 3
Lin, H.-D., Tsai, R., Wen, Y., & Liu, P. (2025) · Antioxidants · doi:10.3390/antiox14121434 · Cited by 3
Bruch’s Membrane: The Critical Boundary in Macular Degeneration
Mullins, R. F., & Elliott, H. (2012) · InTech eBooks · doi:10.5772/31370 · Cited by 2
Uncover molecular network between beta thalassemia and retinal abnormality through in silico study
Sumantri, N. I., Pratama, H., Davida, A., & Rizkinia, M. (2021) · AIP conference proceedings · doi:10.1063/5.0048857 · Cited by 2
Dülger, S. Ç., Çevik, S., Fen, T., & Teke, M. Y. (2024) · International Ophthalmology · doi:10.1007/s10792-024-03029-5 · Cited by 2
Yu, M. D., Bommakanti, N. K., Yonekawa, Y., & Pulido, J. S. (2024) · American Journal of Ophthalmology Case Reports · doi:10.1016/j.ajoc.2024.102154 · Cited by 2
Mechanisms of RDH12-Induced Leber Congenital Amaurosis and Therapeutic Approaches
Kasus‐Jacobi, A., Lea, D., Xu, C. K., Li, F., Wang, H., & Babizhayev, M. A. (2012) · InTech eBooks · doi:10.5772/27243 · Cited by 2
Atypical case of ocular hemosiderosis: Leopard cataract
Masket, S., & Ceran, B. B. (2011) · Journal of Cataract & Refractive Surgery · doi:10.1016/j.jcrs.2011.07.024 · Cited by 2
Effect of the relationship between vitamin C and serum ferritin on fertility.
Al-Katib, S. R., Al-Kaabi, M. M., Al-Safi, W. G., & Al-Bderi, A. J. (2018) · Al-Kufa University Journal for Biology · doi:10.36320/ajb/v10.i1.8207 · Cited by 2
Ocular Biomarkers in Diseases and Toxicities
Kontadakis, G. A., Fragou, D., Plaka, A. D., Hernández, A. F., Kymionis, G. D., & Tsatsakis, A. M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814655-2.00021-9 · Cited by 2
Oxidative stress markers in senile cataract and primary open-angle glaucoma
Nada, W. M., & Moety, D. A. A. (2018) · Delta Journal of Ophthalmology · doi:10.4103/djo.djo_33_17 · Cited by 2
Synthèse intraoculaire de ferritine suite à un corps étranger intraoculaire ferrique
Boukhrissi, F. E., Laktaoui, A., Hommadi, À., Bamou, Y., & Balouch, L. (2017) · Journal Français d Ophtalmologie · doi:10.1016/j.jfo.2016.10.018 · Cited by 1
Lin, Q., Liu, X., Li, X., Yu, J., Luo, W., Rao, Y., & Xie, L. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149606 · Cited by 1
Ferroptosis in diabetic retinopathy: cellular heterogeneity, progression, and therapeutic targets
Liu, C., Zhu, L., Gao, F., Jin, C., Tian, H., Xu, G.-T., Zhang, L., & Lü, L. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-11692-3 · Cited by 1
Sharma, D., Nag, T. C., Bansal, A., Jacob, T. G., Jain, S., & Choudhury, S. D. (2025) · Neurotoxicity Research · doi:10.1007/s12640-025-00752-4 · Cited by 1
El-Sayyad, H., Abou-El-Naga, A. M., Khalifa, S. A., El-Shahari, E. A., & Jala, H. A. N. (2016) · Journal of Drug Metabolism & Toxicology · doi:10.4172/2157-7609.1000219 · Cited by 2
Kurnia, K. H., Elvioza, E., Sidik, M., Sari, T. T., & Sitorus, R. S. (2020) · Retinal Cases & Brief Reports · doi:10.1097/icb.0000000000001038 · Cited by 1
Effect of iron status on fertility of woman in relation with certain hormones and other parameters
Al-Katib, S. R., Al-Kaabi, M. M., Al-Bderi, A. J., & Al-Safi, W. G. (2018) · Al-Kufa University Journal for Biology · doi:10.36320/ajb/v10.i1.8211 · Cited by 1
Protein Oxidation in Some Age‐Related Diseases
Grune, T., Karademir-Yilmaz, B., & Jung, T. (2012) · Wiley eBooks · doi:10.1002/9781118493038.ch4 · Cited by 1
Costa, C. M., Solvas, M. T., García, A. L., Peregort, O. P., & Puig, M. D. C. (2005) · Hispana · Cited by 1
Miscellaneous Iron-Related Disorders
Beaumont, C. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_21
A Case of Retinal Pigmentary Degeneration in PKAN
Jo, S. H., Cheon, C. K., Kim, Y. U., & Jung, J. H. (2013) · Journal of the Korean Ophthalmological Society · doi:10.3341/jkos.2013.54.3.529
Redox mechanisms in retinal cells
Wherry, L. E. (2012) · UEA Digital Repository (University of East Anglia)
Function and pathology of the human retinal pigment epithelium
Booij, J. C. (2010) · UvA-DARE (University of Amsterdam)
Alkhateeb, A. M., Alkhatib, S., Elbetieha, A. M., & Rashaideh, T. A. (2012) · Egyptian Journal of Medical Human Genetics · doi:10.1016/j.ejmhg.2012.10.008
Evaluation of Contrast Sensitivity in Thalassemic Patients
Qazanfari, A., Jafarzadehpur, E., Deilami, K. N., Karami, H., & Mirzajani, A. (2013) · Majallah-i dānishgāh-i ̒ulūm-i pizishkī-i Māzandarān/Journal of Mazandaran University of Medical Sciences
Bourseau, E. (2011) · OpenGrey (Institut de l'Information Scientifique et Technique)
The influence of enviromental and genetic factors on developmnt of glaucoma
Florczak, S., & Kempka, K. (2016) · World Scientific News
The Role of Serum Ceruloplasmin and Oxidative Stress Markers in Primary Open Angle Glaucoma
Sharkh, A. M. A.-S. A., Nada, W. M., Moety, D. A. A., & Elkattawy, H. A. (2018) · Open Journal of Ophthalmology · doi:10.4236/ojoph.2018.81003
N. Fyodorov Eye Microsurgery Federal State Institution of the Russian Ministry of Health, Chuprov, A. D., Треушников, В. М., Notova, S. V., Kim, S. M., N. Fyodorov Eye Microsurgery Federal State Institution of the Russian Ministry of Health, Казакова, Т. В., & Marshinskaia, O. V. (2020) · Trace Elements in Medicine (Moscow) · doi:10.19112/2413-6174-2020-21-4-53-59
Studies on retina-specific gene expression
Reinisalo, M. (2012) · UEF eRepo (University of Eastern Finland)
dos Santos, C. B. A., & Nelson, L. S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813724-6.00060-8
PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in mice retinaPreprint
Zhang, L., Wang, K., Xu, H., Zou, R., Zeng, G., Yuan, Y., Zhu, X., Zhao, X., & Li, J. (2023) · Research Square · doi:10.21203/rs.3.rs-3394581/v1
Research Progress on Protective Effect and Mechanism of Puerarin on Diabetic Retinopathy
(2023) · Journal of Contemporary Medical Practice · doi:10.53469/jcmp.2023.05(11).15
Peng, H., Zhao, L., Wu, P., Lu, J., He, Y., Pan, F., Shu, Q., Wang, X., Xie, H., Ju, H., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3672724/v1
Bakker, L. M., Boulton, M. E., & Rôżanowska, M. (2024) · Antioxidants · doi:10.3390/antiox13111428
Wang, K., Xu, H., Zou, R., Zeng, G., Yuan, Y., Zhu, X., Zhao, X., Li, J., & Zhang, L. (2024) · Figshare · doi:10.6084/m9.figshare.26011954
Wang, K., Xu, H., Zou, R., Zeng, G., Yuan, Y., Zhu, X., Zhao, X., Li, J., & Zhang, L. (2024) · Figshare · doi:10.6084/m9.figshare.26011839
Wang, K., Xu, H., Zou, R., Zeng, G., Yuan, Y., Zhu, X., Zhao, X., Li, J., & Zhang, L. (2024) · Figshare · doi:10.6084/m9.figshare.26732005
Rao, T., Yang, J., Chen, H., & Li, X. (2026) · BMC Ophthalmology · doi:10.1186/s12886-026-04690-3
Giannuzzi, F., Hu, L., Cusato, M., Cestrone, V., Vico, U. D., Caputo, C. G., Rizzo, C., Fede, L. D., Carlà, M. M., Crincoli, E., et al. (2026) · International Ophthalmology · doi:10.1007/s10792-026-04011-z
Management of Traumatic Submacular Hemorrhage by Pneumatic Displacement: A Review
Aljohani, S. M. (2026) · Clinical ophthalmology · doi:10.2147/opth.s592239
Maladie de Parkinson et DMLA : y a-t-il un lien ?
Mathis, T. (2020) · theses.fr (ABES) · doi:10.70675/fa69dd3ez4363z4b07zba8aze1d5251d827b
Rôle du facteur H du complément et du récepteur CD47 dans l’inflammation sous-rétinienne
Augustin, S. (2021) · theses.fr (ABES) · doi:10.70675/be8ffdbez2125z4378za1bbzb8ba72c35267
Imbalanced Trace Elements as Risk Factors in the Pathogenesis of Glaucoma
Steinhorst, K., Lakatos, P., & Hohberger, B. (2026) · Klinische Monatsblätter für Augenheilkunde · doi:10.1055/a-2805-1399
Saeed, A., Naheed, F., Ullah, S., Ullah, A., Taimur, F., Bashir, L., & Afghani, T. (2026) · Hemoglobin · doi:10.1080/03630269.2026.2729184
Protecting Neurons in Retinal and Optic Nerve Diseases: The Role of Ferroptosis-Associated Pathways
Xiang, L., Ye, X., & Lo, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27219601
Metadata
- Authors
- He, X., Hahn, P., Iacovelli, J., Wong, R., King, C., Bhisitkul, R., Massaro-Giordano, M., & Dunaief, J. L.
- Affiliations
- University of Pennsylvania (US)
- University of California, San Francisco (US)
- Corresponding author
- Dunaief, Joshua L.
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 26
- Issue
- 6
- Pages
- 649-673
- ISSN
- 1350-9462 (ISSN-L)
- PMC
- PMC2093950
- OpenAlex
- W2055021524
- Cited by
- 260
- References
- 153
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 18 · 2023: 17 · 2022: 18 · 2021: 19 · 2020: 20 · 2019: 14 · 2018: 15 · 2017: 13 · 2016: 10 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 17
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY 015240, R01EY015240)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- iron homeostasis, retinal degeneration, iron toxicity, oxidative stress, hydroxyl radicals, age-related macular degeneration, ceruloplasmin, transferrin, aceruloplasminemia, Friedreich's ataxia, iron chelation, iron overload, glaucoma, cataract, intraocular hemorrhage
- MeSH terms
- Animals, Biological Transport, Epithelial Cells, Homeostasis, Humans, Iron, Lens, Crystalline, Retina, Retinal Degeneration, Oxidative Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
