Expression of Nitrotyrosine and Oxidative Consequences in the Trabecular Meshwork of Patients with Primary Open-Angle Glaucoma

To evaluate the possible correlation between the visual field defects in patients with primary open-angle glaucoma (POAG) and the expression and enzymatic activity of nitric oxide synthase (NOS) isoenzymes and nitrotyrosine in trabecular meshwork (TM) samples. TM specimens were collected from 146 pa...

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Veröffentlicht in:Investigative ophthalmology & visual science 2008-06, Vol.49 (6), p.2506-2511
Hauptverfasser: Fernandez-Durango, Raquel, Fernandez-Martinez, Amalia, Garcia-Feijoo, Julian, Castillo, Alfredo, de la Casa, Jose Martinez, Garcia-Bueno, Borja, Perez-Nievas, Beatriz G, Fernandez-Cruz, Arturo, Leza, Juan Carlos
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container_end_page 2511
container_issue 6
container_start_page 2506
container_title Investigative ophthalmology & visual science
container_volume 49
creator Fernandez-Durango, Raquel
Fernandez-Martinez, Amalia
Garcia-Feijoo, Julian
Castillo, Alfredo
de la Casa, Jose Martinez
Garcia-Bueno, Borja
Perez-Nievas, Beatriz G
Fernandez-Cruz, Arturo
Leza, Juan Carlos
description To evaluate the possible correlation between the visual field defects in patients with primary open-angle glaucoma (POAG) and the expression and enzymatic activity of nitric oxide synthase (NOS) isoenzymes and nitrotyrosine in trabecular meshwork (TM) samples. TM specimens were collected from 146 patients with POAG by using standard filtration surgery. Visual field defects were evaluated by perimetry. Expression of endothelial (e)NOS and inducible (i)NOS were evaluated by quantitative RT-PCR. Constitutive (Ca2+-dependent) and iNOS (Ca2+-independent) activities were measured by the conversion of L-[14C]-arginine to L-[14C]-citrulline. In four TM specimens from POAG-affected eyes and in three human donor control eyes, 3-nitrotyrosine was localized by immunohistochemistry. The marker of lipid peroxidation malondialdehyde (MDA) was measured by the thiobarbituric acid test in samples of aqueous humor (AH) from 48 patients with either POAG or cataracts. The results showed an upregulation of iNOS and a downregulation of calcium-dependent NOS correlated with visual field defects. Expression and activity of iNOS increased in parallel with visual field defects. However, constitutive activity decreased as the visual field defect increased. Nitrotyrosine was observed only in the cells of the TM specimens from eyes with severe POAG. The increased expression and activity of iNOS in the TM of patients with POAG are proportional to the visual field defect and could lead to the increased of nitrotyrosine levels which may serve as marker of oxidative stress in the progression of cell death of the TM in POAG.
doi_str_mv 10.1167/iovs.07-1363
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TM specimens were collected from 146 patients with POAG by using standard filtration surgery. Visual field defects were evaluated by perimetry. Expression of endothelial (e)NOS and inducible (i)NOS were evaluated by quantitative RT-PCR. Constitutive (Ca2+-dependent) and iNOS (Ca2+-independent) activities were measured by the conversion of L-[14C]-arginine to L-[14C]-citrulline. In four TM specimens from POAG-affected eyes and in three human donor control eyes, 3-nitrotyrosine was localized by immunohistochemistry. The marker of lipid peroxidation malondialdehyde (MDA) was measured by the thiobarbituric acid test in samples of aqueous humor (AH) from 48 patients with either POAG or cataracts. The results showed an upregulation of iNOS and a downregulation of calcium-dependent NOS correlated with visual field defects. Expression and activity of iNOS increased in parallel with visual field defects. However, constitutive activity decreased as the visual field defect increased. Nitrotyrosine was observed only in the cells of the TM specimens from eyes with severe POAG. The increased expression and activity of iNOS in the TM of patients with POAG are proportional to the visual field defect and could lead to the increased of nitrotyrosine levels which may serve as marker of oxidative stress in the progression of cell death of the TM in POAG.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>18296660</pmid><doi>10.1167/iovs.07-1363</doi><tpages>6</tpages></addata></record>
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subjects Aged
Aged, 80 and over
Biological and medical sciences
Calcium - pharmacology
Eye and associated structures. Visual pathways and centers. Vision
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic - physiology
Glaucoma and intraocular pressure
Glaucoma, Open-Angle - metabolism
Humans
Intraocular Pressure
Lipid Peroxidation
Malondialdehyde - metabolism
Medical sciences
Middle Aged
Nitric Oxide Synthase Type II - genetics
Nitric Oxide Synthase Type III - genetics
Ophthalmology
Oxidative Stress - physiology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Trabecular Meshwork - metabolism
Tyrosine - analogs & derivatives
Tyrosine - metabolism
Up-Regulation
Vertebrates: nervous system and sense organs
Vision Disorders - metabolism
Visual Field Tests
Visual Fields
title Expression of Nitrotyrosine and Oxidative Consequences in the Trabecular Meshwork of Patients with Primary Open-Angle Glaucoma
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