Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration

Kimura, Kosuke; Isashiki, Yasushi; Sonoda, Shozo; Kakiuchi-Matsumoto, Tomoko; Ohba, Norio

doi:10.1016/s0002-9394(00)00552-3

Cited by 117 publications

(70 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, no association was established between AMD and the glutathione S-transferase theta 1, glutathione S-transferase mμ 1, and microsomal epoxide hydrolase exon-4 polymorphisms. Allele frequency distribution of all five of these polymorphisms in AMD cases was similar to that found in the Japanese and Caucasian control populations (Kimura et al, 2000). Kimura et al (2000)did, however, report a statistically significant association between a polymorphism in the antioxidant enzyme manganese superoxide dismustase gene (MnSOD) and the exudative form of AMD.…”

Section: Snps Associated With the Oxidative Stress Amd Pathwaysupporting

confidence: 67%

“…Genetic variations within the antioxidants and mechanisms that provide protection against the effects of oxygen toxicity have been the focus of many AMD genetic association studies (For a summary, referTable 3). Kimura et al (2000)screened for polymorphic xenobiotic-metabolizing and antioxidant enzymes in Japanese populations afflicted with exudative (or wet-type) AMD. No association was established between AMD and the two polymorphisms, one located in the 3′ -flanking region and one in exon 4, of the cytochrome P-450 1A1 gene.…”

Section: Snps Associated With the Oxidative Stress Amd Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

Genetic factors of age-related macular degeneration

Tuo

Bojanowski

Chan

2004

Progress in Retinal and Eye Research

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies.

show abstract

Section: Snps Associated With the Oxidative Stress Amd Pathwaysupporting

confidence: 67%

Section: Snps Associated With the Oxidative Stress Amd Pathwaymentioning

confidence: 99%

Genetic factors of age-related macular degeneration

Tuo

Bojanowski

Chan

2004

Progress in Retinal and Eye Research

View full text Add to dashboard Cite

show abstract

“…Some of these activity-altering polymorphisms have been associated with increased risk of cortical cataracts in the human lens, a tissue known to contain GSTP1 and both forms of zeaxanthin (2,42). Whereas the association of risk of age-related macular degeneration with polymorphisms of glutathione S-transferase Mu and Theta isoforms has been examined (43), no comparable studies of GSTP1 polymorphisms have been reported. If rare or common polymorphisms or mutations in GSTP1 decrease the ability of GSTP1 to bind zeaxanthin and other carotenoids, then elevated risk of age-related macular degeneration might be expected due to abnormally low levels of macular carotenoid pigment.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of a Pi Isoform of Glutathione S-Transferase (GSTP1) as a Zeaxanthin-binding Protein in the Macula of the Human Eye

Bhosale

Larson

Frederick

et al. 2004

Journal of Biological Chemistry

249

211

View full text Add to dashboard Cite

Uptake, metabolism, and stabilization of xanthophyll carotenoids in the retina are thought to be mediated by specific xanthophyll-binding proteins (XBPs). A membrane-associated XBP was purified from human macula using ion-exchange chromatography followed by gel-exclusion chromatography. Two-dimensional gel electrophoresis showed a prominent spot of 23 kDa and an isoelectric point of 5.7. Using mass spectral sequencing methods and the public NCBI database, it was identified as a Pi isoform of human glutathione S-transferase (GSTP1). Dietary (3R,3 R)-zeaxanthin displayed the highest affinity with an apparent K d of 0. Other mammalian xanthophyll carrier proteins such as tubulin, high-density lipoprotein, low-density lipoprotein, albumin, and ␤-lactoglobulin did not bind zeaxanthins with high affinity, and they failed to induce or alter xanthophyll CD spectra to any significant extent. Immunocytochemistry with an antibody to GSTP1 on human macula sections showed highest labeling in the outer and inner plexiform layers. These results indicate that GSTP1 is a specific XBP in human macula that interacts with (3R,3 S-meso)-zeaxanthin and dietary (3R,3 R)-zeaxanthin in contrast to apparently weaker interactions with (3R,3 R,6 R)-lutein.

show abstract

“…Hypopigmentation and altered expression of Mitf and Mitf-regulated downstream gene targets have been observed following experimental induction of oxidative stress (Jimenez-Cervantes et al, 2001). Iron overload has been implicated in the pathogenesis of age-related macular degeneration (ARMD) in human patients and in mouse models (Chowers et al, 2006;Dentchev et al, 2005;Dunaief et al, 2005;Hahn et al, 2004), and polymorphisms in microsomal epoxide hydrolase (Ephx1) have also been associated with ARMD (Kimura et al, 2000). Altered expression of Gpnmb, Mlana,Nramp1, and Ephx1 may therefore be involved in the RPE pathology observed in Mitf vit/vit mutants.…”

Section: Discussionmentioning

confidence: 99%

Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal development of the retinal pigment epithelium in microphthalmia-associated transcription factor Mitfmi and Mitfvitiligo mouse mutants

Waes

Smith

Waes

et al. 2008

Experimental Eye Research

View full text Add to dashboard Cite

Microphthalmia-associated Transcription Factor (Mitf) is expressed in neural crest cell-derived melanocytes, and in the retinal pigment epithelium (RPE) during ocular development. Mutations in Mitf are associated with auditory/visual/pigmentary syndromes in humans. Mitf mi/mi mouse mutants lack pigmentation, and are microphthalmic, while Mitf vit/vit mouse mutants display abnormal RPE pigmentation, and progressive retinal degeneration. Microarray analysis was used to identify novel downstream gene targets/pathways in the RPE that are altered by mutations in the transcription factor Mitf. Using the Affymetrix platform, gene expression profiles were generated using the eyes of E13.5 mouse fetuses that were wildtype, heterozygous, or homozygous for the Mitf mi mutation. In a separate experiment, eyes from E13.5 mouse fetuses homozygous for the Mitf vit mutation were compared to eyes from the C57BL/6 control background strain. Statistical analyses were performed using Robust Multiarray Average, mixed-effects ANOVA and random-variance t-tests. Altered expression of genes involved in pigment formation, melanosome biogenesis/transport, and redox homeostasis were observed. 12 genes were commonly mis-regulated in the eyes of both Mitf mutants: 10 of these genes were downregulated in both mutants relative to controls, while 2 of the genes (Nramp1 (Slc11a1) and epoxide hydrolase) were downregulated in Mitf mi/mi mutants, and conversely, upregulated in Mitf vit/vit mutants. Quantitative RT-PCR and immunohistochemistry were used to confirm altered gene/protein expression. RPE expression of the Fe +2 iron transporter Nramp1 (Slc11a1) has not previously been reported. Fe +2 is an important co-factor utilized by the iron-dependent isomerohydrolase RPE65 in the retinoid visual cycle. However, excess accumulation of Fe +2 in the RPE has recently been associated with oxidative damage and age-related macular degeneration. Abnormal pigmentation and increased activity of Slc11a1 in the RPE of Mitf vit mice may contribute to the pathology and progressive retinal degeneration observed in these mutants.

show abstract

Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration

Cited by 117 publications

References 11 publications

Genetic factors of age-related macular degeneration

Genetic factors of age-related macular degeneration

Identification and Characterization of a Pi Isoform of Glutathione S-Transferase (GSTP1) as a Zeaxanthin-binding Protein in the Macula of the Human Eye

Altered expression of the iron transporter Nramp1 (Slc11a1) during fetal development of the retinal pigment epithelium in microphthalmia-associated transcription factor Mitfmi and Mitfvitiligo mouse mutants

Contact Info

Product

Resources

About