Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress

Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the anti...

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Veröffentlicht in:Human gene therapy 2004-10, Vol.15 (10), p.960-967
Hauptverfasser: REX, T. S, TSUI, I, HAHN, P, MAGUIRE, A. M, DUAN, D, BENNETT, J, DUNAIEF, J. L
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container_end_page 967
container_issue 10
container_start_page 960
container_title Human gene therapy
container_volume 15
creator REX, T. S
TSUI, I
HAHN, P
MAGUIRE, A. M
DUAN, D
BENNETT, J
DUNAIEF, J. L
description Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. To test this hypothesis, we transduced retinal pigment epithelial (RPE) cells in vitro and in vivo with adenovirus carrying the catalase gene (Ad.CMV.catalase). After transduction of only a subset of RPE cells in vitro, all cells in the culture were protected from exogenous hydrogen peroxide. Similarly, in vivo, eyes injected with Ad. CMV. catalase had high catalase levels in the RPE, which protected the adjacent photoreceptors from light damage and reduced photoreceptor oxidative stress as measured by the markers 4-hydroxynonenal and nitrotyrosine. Both in vitro and in vivo, gene therapy with Ad. CMV. catalase protected neighboring cells from oxidative stress-induced terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity. The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells.
doi_str_mv 10.1089/hum.2004.15.960
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S ; TSUI, I ; HAHN, P ; MAGUIRE, A. M ; DUAN, D ; BENNETT, J ; DUNAIEF, J. L</creator><creatorcontrib>REX, T. S ; TSUI, I ; HAHN, P ; MAGUIRE, A. M ; DUAN, D ; BENNETT, J ; DUNAIEF, J. L</creatorcontrib><description>Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. To test this hypothesis, we transduced retinal pigment epithelial (RPE) cells in vitro and in vivo with adenovirus carrying the catalase gene (Ad.CMV.catalase). After transduction of only a subset of RPE cells in vitro, all cells in the culture were protected from exogenous hydrogen peroxide. Similarly, in vivo, eyes injected with Ad. CMV. catalase had high catalase levels in the RPE, which protected the adjacent photoreceptors from light damage and reduced photoreceptor oxidative stress as measured by the markers 4-hydroxynonenal and nitrotyrosine. Both in vitro and in vivo, gene therapy with Ad. CMV. catalase protected neighboring cells from oxidative stress-induced terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity. The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2004.15.960</identifier><identifier>PMID: 15585111</identifier><identifier>CODEN: HGTHE3</identifier><language>eng</language><publisher>Larchmont, NY: Liebert</publisher><subject>Adenoviridae - genetics ; Adenovirus ; Aldehydes - chemistry ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biotechnology ; Catalase - genetics ; Catalase - metabolism ; Cell Membrane - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Gene Transfer Techniques ; Genetic Therapy - methods ; Health. Pharmaceutical industry ; Humans ; Hydrogen Peroxide - chemistry ; Hydrogen Peroxide - pharmacology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Industrial applications and implications. Economical aspects ; Light ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Microscopy, Confocal ; Oxidative Stress ; Photoreceptor Cells - metabolism ; Pigment Epithelium of Eye - metabolism ; Retina - metabolism ; Transfusions. Complications. Transfusion reactions. 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S</creatorcontrib><creatorcontrib>TSUI, I</creatorcontrib><creatorcontrib>HAHN, P</creatorcontrib><creatorcontrib>MAGUIRE, A. M</creatorcontrib><creatorcontrib>DUAN, D</creatorcontrib><creatorcontrib>BENNETT, J</creatorcontrib><creatorcontrib>DUNAIEF, J. L</creatorcontrib><title>Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. 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The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells.</description><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>Aldehydes - chemistry</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Catalase - genetics</subject><subject>Catalase - metabolism</subject><subject>Cell Membrane - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Health. Pharmaceutical industry</subject><subject>Humans</subject><subject>Hydrogen Peroxide - chemistry</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Light</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microscopy, Confocal</subject><subject>Oxidative Stress</subject><subject>Photoreceptor Cells - metabolism</subject><subject>Pigment Epithelium of Eye - metabolism</subject><subject>Retina - metabolism</subject><subject>Transfusions. Complications. Transfusion reactions. 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source Mary Ann Liebert Online Subscription; MEDLINE
subjects Adenoviridae - genetics
Adenovirus
Aldehydes - chemistry
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Applied cell therapy and gene therapy
Biological and medical sciences
Biotechnology
Catalase - genetics
Catalase - metabolism
Cell Membrane - metabolism
Fundamental and applied biological sciences. Psychology
Gene therapy
Gene Transfer Techniques
Genetic Therapy - methods
Health. Pharmaceutical industry
Humans
Hydrogen Peroxide - chemistry
Hydrogen Peroxide - pharmacology
Immunohistochemistry
In Situ Nick-End Labeling
Industrial applications and implications. Economical aspects
Light
Male
Medical sciences
Mice
Mice, Inbred BALB C
Microscopy, Confocal
Oxidative Stress
Photoreceptor Cells - metabolism
Pigment Epithelium of Eye - metabolism
Retina - metabolism
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
title Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress
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