Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure
Open accessAbstract
Because as many as half of glaucoma patients on intraocular pressure (IOP)-lowering therapy continue to experience optic nerve toxicity, it is imperative to find other effective therapies. Iron and calcium ions play key roles in oxidative stress, a hallmark of glaucoma. Therefore, we tested metal chelation by means of ethylenediaminetetraacetic acid (EDTA) combined with the permeability enhancer methylsulfonylmethane (MSM) applied topically on the eye to determine if this noninvasive treatment is neuroprotective in rat optic nerve and retinal ganglion cells exposed to oxidative stress induced by elevated IOP. Hyaluronic acid (HA) was injected into the anterior chamber of the rat eye to elevate the IOP. EDTA-MSM was applied topically to the eye for 3 months. Eyeballs and optic nerves were processed for histological assessment of cytoarchitecture. Protein-lipid aldehyde adducts and cyclooxygenase-2 (COX-2) were detected immunohistochemically. HA administration increased IOP and associated oxidative stress and inflammation. Elevated IOP was not affected by EDTA-MSM treatment. However, oxidative damage and inflammation were ameliorated as reflected by a decrease in formation of protein-lipid aldehyde adducts and COX-2 expression, respectively. Furthermore, EDTA-MSM treatment increased retinal ganglion cell survival and decreased demyelination of optic nerve compared with untreated eyes. Chelation treatment with EDTA-MSM ameliorates sequelae of IOP-induced toxicity without affecting IOP. Because most current therapies aim at reducing IOP and damage occurs even in the absence of elevated IOP, EDTA-MSM has the potential to work in conjunction with pressure-reducing therapies to alleviate damage to the optic nerve and retinal ganglion cells.
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In an in vivo rat model, topically administered EDTA combined with a permeability enhancer reduced signs of oxidative stress and inflammation in glaucoma, increased retinal ganglion cell survival, and decreased demyelination of the optic nerve compared with untreated eyes.
“The topically administered metal chelator, EDTA, combined with a permeability enhancer reduced signs of oxidative stress and inflammation in glaucoma in the rat's eyes, increased retinal ganglion cell survival, and decreased demyelination of optic nerve compared with untreated eyes [69].”
From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [69]
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The utility of iron chelators in the management of inflammatory disorders
Lehmann, C., Islam, S., Jarosch, S., Zhou, J., Hoskin, D., Greenshields, A., Al-Banna, N., Sharawy, N., Sczcesniak, A., Kelly, M., et al. (2015) · Mediators of Inflammation · doi:10.1155/2015/516740 · Cited by 54 · see citing works
- Authors
- Liu, P., Zhang, M., Shoeb, M., Hogan, D., Tang, L., Syed, M. F., Wang, C. Z., Campbell, G. A., & Ansari, N. H.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Central South University (CN)
- Corresponding author
- Ansari, N.H.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 69
- Pages
- 289-299
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC4005814
- OpenAlex
- W1974476087
- Cited by
- 28
- References
- 66
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 4 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 3
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY13014)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- glaucoma, intraocular pressure elevation, oxidative stress, metal chelation, EDTA, methylsulfonylmethane, topical ocular therapy, retinal ganglion cells, demyelination, cyclooxygenase-2, inflammation, hyaluronic acid
- MeSH terms
- Animals, Chelating Agents, Dimethyl Sulfoxide, Edetic Acid, Glaucoma, Humans, Optic Nerve, Permeability, Retinal Ganglion Cells, Sulfones, Oxidative Stress, Neuroprotective Agents, Intracranial Hypertension, Rats
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