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Iron is neurotoxic in retinal detachment and transferrin confers neuroprotection.
- Source :
-
Science advances [Sci Adv] 2019 Jan 09; Vol. 5 (1), pp. eaau9940. Date of Electronic Publication: 2019 Jan 09 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- In retinal detachment (RD), photoreceptor death and permanent vision loss are caused by neurosensory retina separating from the retinal pigment epithelium because of subretinal fluid (SRF), and successful surgical reattachment is not predictive of total visual recovery. As retinal iron overload exacerbates cell death in retinal diseases, we assessed iron as a predictive marker and therapeutic target for RD. In the vitreous and SRF from patients with RD, we measured increased iron and transferrin (TF) saturation that is correlated with poor visual recovery. In ex vivo and in vivo RD models, iron induces immediate necrosis and delayed apoptosis. We demonstrate that TF decreases both apoptosis and necroptosis induced by RD, and using RNA sequencing, pathways mediating the neuroprotective effects of TF are identified. Since toxic iron accumulates in RD, we propose TF supplementation as an adjunctive therapy to surgery for improving the visual outcomes of patients with RD.
- Subjects :
- Aged
Animals
Apoptosis drug effects
Disease Models, Animal
Eye Diseases, Hereditary surgery
Female
Humans
Iron pharmacology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Middle Aged
Necrosis
Photoreceptor Cells, Vertebrate metabolism
Rats
Rats, Long-Evans
Rats, Wistar
Retina metabolism
Retinal Detachment surgery
Retinal Pigment Epithelium metabolism
Subretinal Fluid metabolism
Transferrin genetics
Eye Diseases, Hereditary metabolism
Iron metabolism
Iron toxicity
Neuroprotection
Retinal Detachment metabolism
Transferrin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 5
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 30662950
- Full Text :
- https://doi.org/10.1126/sciadv.aau9940