SOD2 Protects against Oxidation-Induced Apoptosis in Mouse Retinal Pigment Epithelium: Implications for Age-Related Macular Degeneration

Kasahara, Emiko; Lin, Lishan; Ho, Ye-Shih; Reddy, Venkat N.

doi:10.1167/iovs.05-0344

Cited by 91 publications

(79 citation statements)

References 34 publications

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“…Animal experiments showed that manganese SOD2 knockdown in mice resulted in apoptotic death of RPE cells, which was similar to the eyes of patients with AMD [21]. SOD2 protects against oxidation-induced apoptosis in mouse RPE [22]. This implies that SOD may be an important antioxidative enzyme in protecting RPE against oxidant-induced damage.…”

Section: Discussionmentioning

confidence: 90%

Effect of (R)-α-Lipoic Acid Supplementation on Serum Lipids and Antioxidative Ability in Patients with Age-Related Macular Degeneration

et al. 2012

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Background/Aims: Supplementation with antioxidants is of special interest in preventing or delaying the development and progression of age-related macular degeneration (AMD). This investigation aimed to assess the effect of α- lipoic acid (LA) on serum lipids, serum malondialdehyde (MDA) and superoxide dismutase (SOD) in patients with AMD. Methods: A total of 62 patients (50–75 years old) with early and intermediate dry form of AMD were randomly assigned to two groups, i.e. LA administration (n = 32) and placebo (n = 30). The levels of serum lipids and MDA and SOD activity were measured before and after LA and placebo intervention. Results: Compared with the parameters at baseline, serum total cholesterol (CHO), triglyceride and high- and low-density lipoprotein CHO (HDL and LDL) levels were not significantly different after LA and placebo intervention. There was a slight but statistically nonsignificant decrease in serum MDA levels and a statistically significant increase in serum SOD activity after LA intervention. There were no statistically significant differences in serum MDA levels or SOD activity after placebo intervention. Conclusion: The apparent increase in SOD activity caused by LA supplementation indicates that LA may have a possible preventive effect in the development of AMD through an antioxidant mechanism.

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Section: Discussionmentioning

confidence: 90%

Effect of (R)-α-Lipoic Acid Supplementation on Serum Lipids and Antioxidative Ability in Patients with Age-Related Macular Degeneration

et al. 2012

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“…SOD2 overexpression eliminates pro-oxidantinduced mitochondrial ROS in PC-12 cells and decreases cell injury (Pias et al, 2003). Similarly, in retinal pigment epithelial cells, the gene dosage of SOD2 directly relates to the degree of mitochondrial injury and apoptosis induced by H 2 O 2 (Kasahara et al, 2005). In hemopoietic cells, SOD2 transgene decreases ionizing radiation-induced mitochondrial membrane permeability, cytochrome c release and caspase-3 activation (Guo et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

SOD2 protects neurons from injury in cell culture and animal models of diabetic neuropathy

Vincent

Russell

Sullivan

et al. 2007

Experimental Neurology

102

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Hyperglycemia-induced oxidative stress is an inciting event in the development of diabetic complications including diabetic neuropathy. Our observations of significant oxidative stress and morphological abnormalities in mitochondria led us to examine manganese superoxide dismutase (SOD2), the enzyme responsible for mitochondrial detoxification of oxygen radicals. We demonstrate that over expression of SOD2 decreases superoxide (O 2 •− ) in cultured primary dorsal root ganglion (DRG) neurons and subsequently blocks caspase-3 activation and cellular injury. Under expression of SOD2 in dissociated DRG cultures from adult SOD2 +/− mice results in increased levels of O 2 •− , activation of caspase-3 cleavage and decreased neurite outgrowth under basal conditions that are exacerbated by hyperglycemia. These profound changes in sensory neurons led us to explore the effects of decreased SOD2 on the development of diabetic neuropathy (DN) in mice. DN was assessed in SOD2 +/− C57BL/6J mice and their SOD2 +/+ litter mates following streptozotocin (STZ) treatment. These animals, while hyperglycemic, do not display any signs of DN. DN was observed in the C57BL/6Jdb/db mouse, and decreased expression of SOD2 in these animals increased DN. Our data suggest that SOD2 activity is an important cellular modifier of neuronal oxidative defense against hyperglycemic injury.

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“…Mice deficient in SOD 1 have features typical of AMD, older mice exhibited drusen accumulation, thickened Bruch's membrane and choroidal neovascularization (Imamura et al, 2006). SOD 2 was shown to protect against oxidation induced apoptosis in RPE cells from wild type, hemizygous and heterozygous SOD 2 mice (Kasahara, et al, 2005). Reddy et al (2004) found that in SOD 2 deficient lens epithelial cells challenged with superoxide there were dramatic mitochondrial changes, cytochrome C leakage, caspase 3 activation and increased apoptotic death.…”

Section: Mitochondrial Protective and Repair Systemsmentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

162

141

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Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al., 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (˙OH), hydrogen peroxide (H 2 O 2 ) and peroxynitrite (OONO -). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria (Hansford et al., 1997). Generation of superoxide at complex I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane (Kakkar and Singh 2007). While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr)

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SOD2 Protects against Oxidation-Induced Apoptosis in Mouse Retinal Pigment Epithelium: Implications for Age-Related Macular Degeneration

Abstract: The results demonstrate a critical role of SOD2 in protection against oxidative challenge. Cells from HET mice showed greater apoptotic cell death, whereas in those from HEMI mice, cell death induced by oxidative injury was suppressed.

Cited by 91 publications

References 34 publications

Effect of (R)-α-Lipoic Acid Supplementation on Serum Lipids and Antioxidative Ability in Patients with Age-Related Macular Degeneration

Effect of (R)-α-Lipoic Acid Supplementation on Serum Lipids and Antioxidative Ability in Patients with Age-Related Macular Degeneration

SOD2 protects neurons from injury in cell culture and animal models of diabetic neuropathy

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

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