Oxidative Damage in the Retinal Mitochondria of Diabetic Mice: Possible Protection by Superoxide Dismutase
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PURPOSE: Superoxide levels are elevated in the retina in patients with diabetes, and cytochrome c is released from the mitochondria. The purpose of this study was to elucidate the mechanism involved in the oxidative damage of retinal mitochondria in diabetes and to determine whether mitochondrial superoxide dismutase (MnSOD) provides protection. METHODS: Effects of diabetes were investigated on superoxide and GSH levels, electron transport complexes I and III, and membrane permeability in the isolated mitochondria prepared from the retinas of streptozotocin diabetic mice. To investigate the effect of MnSOD, retinal mitochondrial oxidative stress and electron transport complexes were determined in mice overexpressing MnSOD (MnSOD-Tg). Histopathology was evaluated in trypsin-digested retina. RESULTS: Retinal mitochondria had twofold increase in superoxide levels in nontransgenic (wild-type [WT]) diabetic mice compared with WT nondiabetic mice. In the same retina, diabetes decreased mitochondrial GSH levels by 40% and complex III activity by approximately 20%, and it increased mitochondrial membrane permeability (swelling) by more than twofold; however, complex I activity was not affected. Overexpression of MnSOD inhibited diabetes-induced increases in mitochondrial superoxide levels and membrane permeability and the decrease in complex III activity. GSH values, however, were not statistically different in WT and MnSOD-Tg diabetic mice. In contrast to the diabetes-induced increase in the number of degenerate (acellular) capillaries in WT diabetic mice, the numbers of acellular capillaries in MnSOD-Tg nondiabetic and diabetic mice were similar to those in WT nondiabetic mice. CONCLUSIONS: Retinal mitochondria experience increased oxidative damage in diabetes, and complex III is one of the sources of increased superoxide. MnSOD protects the retina from diabetes-induced abnormalities in the mitochondria and prevents vascular histopathology, strongly implicating the role for MnSOD in the pathogenesis of retinopathy in diabetes.
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Superoxide production, measured as lucigenin fluorescence, was increased in retinal tissue isolated from streptozotocin-diabetic mice with blood glucose concentrations ∼400 mg/dl.
“Kanwar et al. (156) reported that superoxide production, measured as lucigenin fluorescence, was increased in retinal tissue isolated from streptozotocin-diabetic mice with blood glucose concentrations ∼400 mg/dl.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [156]
Overexpression of MnSOD in diabetic mice prevented the increase in retinal superoxide production.
“This was prevented by overexpression of MnSOD in the diabetic mice before isolation of the retinal tissue.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [156]
Diabetes decreased mitochondrial content of reduced glutathione in retinal tissue.
“These authors also reported that diabetes decreased mitochondrial content of reduced glutathione.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [156]
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- Authors
- Kanwar, M., Chan, P.-S., Kern, T. S., & Kowluru, R. A.
- Affiliations
- Wayne State University (US)
- Case Western Reserve University (US)
- ORCID
- Kern, Timothy S.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2007-08-01
- Volume
- 48
- Issue
- 8
- Pages
- 3805
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2011158839
- Cited by
- 333
- References
- 36
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 8 · 2023: 16 · 2022: 17 · 2021: 21 · 2020: 21 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 20 · 2015: 25 · 2014: 23 · 2013: 17 · 2012: 18
- FWCI
- 18.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- diabetic retinopathy, retinal mitochondria, oxidative stress, superoxide, manganese superoxide dismutase, cytochrome c release, mitochondrial membrane permeability, glutathione, acellular capillaries, streptozotocin-induced diabetes
- MeSH terms
- Superoxide Dismutase 2, Animals, Capillaries, Diabetic Retinopathy, Female, Glutathione, Hyperglycemia, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Mitochondrial Swelling, Retina, Retinal Vessels, Superoxides, Superoxide Dismutase, Electron Transport Complex III, Oxidative Stress, Electron Transport Complex I, Mitochondrial Membranes, Mice
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