title: Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure.
abstract: 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.
authors: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
authors: P
authors: P
authors: Liu
authors: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
authors: M
authors: M
authors: Zhang
authors: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
authors: M
authors: M
authors: Shoeb
authors: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
authors: D
authors: D
authors: Hogan
authors: Ophthalmology Department, Second Xiangya Hospital, Central South University, Changsha 410011, People's Republic of China.
authors: Luosheng
authors: L
authors: Tang
authors: Department of Ophthalmology & Visual Science, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
authors: M F
authors: MF
authors: Syed
authors: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
authors: C Z
authors: CZ
authors: Wang
authors: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
authors: G A
authors: GA
authors: Campbell
authors: Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA. Electronic address: nansari@utmb.edu.
authors: N H
authors: NH
authors: Ansari
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage*; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage*; D004492:Edetic Acid / Q000008:administration & dosage*; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D019586:Intracranial Hypertension / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects; D013450:Sulfones / Q000008:administration & dosage*
chemical_list: D002614:Chelating Agents; D018696:Neuroprotective Agents; D013450:Sulfones; D004492:Edetic Acid; C025910:dimethyl sulfone; D004121:Dimethyl Sulfoxide
keywords: Chelation therapy; EDTA; Free radicals; Glaucoma; Glaucomatous neurodegeneration; Hyaluronic acid; Inflammation; Intraocular pressure; Metal chelation; Methylsulfonylmethane; Ocular hypertension; Oxidative damage; Oxidative stress; Reactive oxygen species; Retinal ganglion cell