Systemic administration of the iron chelator deferiprone protects against light-induced photoreceptor degeneration in the mouse retina
Open accessAbstract
Oxidative stress plays a key role in a light-damage (LD) model of retinal degeneration as well as in age-related macular degeneration (AMD). Since iron can promote oxidative stress, the iron chelator deferiprone (DFP) was tested for protection against light-induced retinal degeneration. To accomplish this, A/J mice were treated with or without oral DFP and then were placed in constant bright white fluorescent light (10,000 lx) for 20 h. Retinas were evaluated at several time points after light exposure. Photoreceptor apoptosis was assessed using the TUNEL assay. Retinal degeneration was assessed by histology 10 days after exposure to damaging white light. Two genes upregulated by oxidative stress, heme oxygenase 1 (Hmox1) and ceruloplasmin (Cp), as well as complement component 3 (C3) were quantified by RT-qPCR. Cryosections were immunolabeled for an oxidative stress marker (nitrotyrosine), a microglial marker (Iba1), as well as both heavy (H) and light (L) ferritin. Light exposure resulted in substantial photoreceptor-specific cell death. Dosing with DFP protected photoreceptors, decreasing the numbers of TUNEL-positive photoreceptors and increasing the number of surviving photoreceptors. The retinal mRNA levels of oxidative stress-related genes and C3 were upregulated following light exposure and diminished by DFP treatment. Immunostaining for nitrotyrosine indicated that DFP reduced the nitrative stress caused by light exposure. Robust H/L-ferritin-containing microglial activation and migration to the outer retina occurred after light exposure and DFP treatment reduced microglial invasion. DFP is protective against light-induced retinal degeneration and has the potential to diminish oxidative stress in the retina.
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These effects along with oxidative stress to photoreceptors can be prevented by the oral iron chelator DFP.
“These effects along with oxidative stress to photoreceptors can be prevented by the oral iron chelator DFP [217].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [217]
Experimental light damage to the retina results in microglial activation, migration to the outer retina, and induction of ferritin H and L chains.
“In addition, experimental light damage to the retina results in microglial activation, its migration to the outer retina, and in induction of FT H and L chains.”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [217]
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Self-citation
- Authors
- Song, D., Song, Y., Hadziahmetovic, M., Zhong, Y., & Dunaief, J. L.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- University of Pennsylvania (US)
- Corresponding author
- Dunaief, Joshua L.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 53
- Issue
- 1
- Pages
- 64-71
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC3380452
- OpenAlex
- W1998946447
- Cited by
- 96
- References
- 59
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 10 · 2014: 15 · 2013: 6 · 2012: 2
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R01EY015240)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular and Laser Science Research
- Keywords
- deferiprone, iron chelation, light-induced retinal degeneration, photoreceptor apoptosis, oxidative stress, nitrative stress, nitrotyrosine, microglial activation, ferritin, heme oxygenase-1, ceruloplasmin, complement C3, age-related macular degeneration, photoprotection
- MeSH terms
- Deferiprone, Animals, Female, Fluorescent Antibody Technique, Iron Chelating Agents, Light, Mice, Inbred A, Pyridones, Radiation Injuries, Experimental, Retinal Degeneration, RNA, Messenger, Apoptosis, Microglia, Oxidative Stress, Reverse Transcriptase Polymerase Chain Reaction, In Situ Nick-End Labeling, Photoreceptor Cells, Vertebrate, Mice, Real-Time Polymerase Chain Reaction
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