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Effect of Long-Term Administration of α-Lipoic Acid on Retinal Capillary Cell Death and the Development of Retinopathy in Diabetic Rats
Open accessAbstract
Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. α-Lipoic acid, a thiol antioxidant, has been shown to have beneficial effects on polyneuropathy and on the parameters of oxidative stress in various tissues, including nerve, kidney, and retina. The purpose of this study was to examine the effect of α-lipoic acid on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without α-lipoic acid (400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of α-lipoic acid administration on retinal 8-hydroxy-2′deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked immunosorbent assay. α-Lipoic acid administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the two diabetic groups (with and without α-lipoic acid). Retinal 8-OHdG and nitrotyrosine levels were increased by over twofold and 70%, respectively, in diabetes, and α-lipoic acid administration inhibited these increases. Our results demonstrate that the long-term administration of α-lipoic acid has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. α-Lipoic acid supplementation represents an achievable adjunct therapy to help prevent vision loss in diabetic patients.
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“α-Lipoic acid also protected the retinal microvasculature in diabetic rats by reducing nitrotyrosine and oxidized DNA (174).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [174]
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Vascular endothelial growth factor in eye disease
Penn, J. S., Madan, A., Caldwell, R. B., Bartoli, M., Caldwell, R. W., & Hartnett, M. E. (2008) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2008.05.001 · Cited by 784
Oxidative Stress and Diabetic Retinopathy
Kowluru, R. A., & Chan, P.-S. (2007) · Journal of Diabetes Research · doi:10.1155/2007/43603 · Cited by 772
Self-citationSivitz, W. I., & Yorek, M. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2531 · Cited by 742
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Metadata
- Authors
- Kowluru, R. A., & Odenbach, S.
- Affiliations
- Wayne State University (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-12-01
- Volume
- 53
- Issue
- 12
- Pages
- 3233-3238
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2095953797
- Cited by
- 227
- References
- 73
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 16 · 2021: 6 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 13 · 2016: 7 · 2015: 7 · 2014: 12 · 2013: 15 · 2012: 15
- FWCI
- 11.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- alpha-lipoic acid, diabetic retinopathy, apoptosis, oxidative stress, 8-hydroxy-2'-deoxyguanosine, nitrotyrosine, streptozotocin-induced diabetes, thiol antioxidants, acellular capillaries, hyperglycemia, blindness prevention
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Diabetic Retinopathy, Thioctic Acid, Male, Retina, Retinal Vessels, Cell Death, Rats, Wistar, Oxidative Stress, Rats
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