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Enhanced age-related cataract in copper-zinc superoxide dismutase null mice
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
2012 (Engelska)Ingår i: Clinical and Experimental Ophthalmology, ISSN 1442-6404, E-ISSN 1442-9071, Vol. 40, nr 8, s. 813-820Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: As the lens is constantly exposed to light and oxygen that generate harmful reactive oxygen species, the importance of the intracellular antioxidant enzyme copper-zinc superoxide dismutase for the protection against age-related cataract development was explored.

Methods: The development of lens opacities and the lens oxidative status were studied in different age groups of mice lacking copper-zinc superoxide dismutase and in wild-type mice. The lens opacities were quantified from lens photographs using digital image analysis. Thereafter, the lenses were homogenized and analysed regarding their contents of reduced glutathione and protein carbonyls suggestive of protein oxidation.

Results: The 18-week-old mice of both genotypes had clear lenses. At 1 year of age, the copper-zinc superoxide dismutase null mice had developed cortical lens opacities, whereas the wild-type mice did not show equivalent changes until 2 years of age. The lens contents of glutathione decreased only in the 2-year-old wild-type mice, whereas the carbonyls increased over time without any differences between the two genotypes.

Conclusions: This study indicates that the lack of copper-zinc superoxide dismutase may accelerate age-related lens opacity development and that intracellular superoxide-derived oxidative stress may be damaging to the lens during ageing. Participation of the anti-oxidant enzyme copper-zinc superoxide dismutase in the protection against age-related cataract was thus suggested.

Ort, förlag, år, upplaga, sidor
Wiley-Blackwell, 2012. Vol. 40, nr 8, s. 813-820
Nationell ämneskategori
Oftalmologi
Forskningsämne
oftalmiatrik
Identifikatorer
URN: urn:nbn:se:umu:diva-21028DOI: 10.1111/j.1442-9071.2012.02794.xOAI: oai:DiVA.org:umu-21028DiVA, id: diva2:210406
Tillgänglig från: 2009-04-01 Skapad: 2009-04-01 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Superoxide dismutase 1 and cataract
Öppna denna publikation i ny flik eller fönster >>Superoxide dismutase 1 and cataract
2009 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Light and oxygen generate harmful reactive oxygen species (ROS) in the lens, causing biochemical changes that gradually disarrange the lens fibres resulting in light scattering and loss of transparency. In the healthy eye, this chronic exposure to oxidative stress may lead to age-related cataract. However, there are also some conditions that accelerate cataract formation, such as diabetes mellitus, in which increased glucose levels may contribute to increased generation of ROS.

The superoxide dismutases (SOD) participate in the defence against ROS by catalysing the dismutation of superoxide radicals. The main SOD isoenzyme in the lens is copper-zinc superoxide dismutase (SOD1). The aim of this thesis was to explore if this antioxidant enzyme is important for the protection against age-related and diabetes-induced cataract development.

Lenses from wild-type mice and mice lacking SOD1 were incubated in high levels of glucose in vitro and their transparency and damage evaluated daily. Also, the impact of nitric oxide was studied by adding a nitric oxide synthase inhibitor. Furthermore, in vivo cataract formation in relation to the oxidative status of the lens was evaluated in streptozotocin-induced diabetic mice as well as in non-diabetic mice of both genotypes. Finally, the spontaneous age-related cataract development was studied in both genotypes.

In vitro, the SOD1 null lenses showed increased levels of superoxide radicals and developed dense nuclear lens opacities upon exposure to high levels of glucose. They also showed increased lens leakage of lactate dehydrogenase, reduced transport function across cell membranes, and increased water contents. However, the lens damage and cataract formation were eliminated when the synthesis of nitric oxide was inhibited. This indicates that both superoxide and nitric oxide have important roles in glucose-induced cataract development possibly through their reaction with each other which generates the highly reactive peroxynitrite.

In vivo, both the SOD1 null and the wild-type mice showed cortical cataract changes after 8 weeks of diabetes, although the SOD1 null mice showed a more pronounced cataract formation than the wild-type mice in relation to the level of hyperglycaemia. As cataract formation was accentuated the lenses showed diminishing levels of glutathione but increasing amounts of protein carbonyls, suggesting a reduced lens antioxidant capacity as well as increased lens protein oxidation. Non-diabetic young (18 weeks of age) SOD1 null mice did not show any signs of cataract. At 1 year of age they had developed some cortical lens obscurity as compared to the wild-type mice which did not show equivalent changes until 2 years of age.

The results presented in this thesis show that SOD1 null mice are more prone to develop diabetes-induced and age-related cataract than wild-type mice. The findings thus further endorse the importance of oxidative stress as a contributor to cataract development and indicate that both superoxide and nitric oxide may be damaging to the lens. I therefore conclude that the antioxidant enzyme SOD1 is important for the protection against cataract.

Ort, förlag, år, upplaga, sidor
Umeå: Institutionen för klinisk vetenskap, 2009. s. 76
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1254
Nyckelord
cataract, diabetes mellitus, nitric oxide, superoxide, superoxide dismutase, SOD1 null mice
Nationell ämneskategori
Oftalmologi
Forskningsämne
oftalmiatrik
Identifikatorer
urn:nbn:se:umu:diva-21032 (URN)978-91-7264-749-7 (ISBN)
Distributör:
Oftalmiatrik, 901 87, Umeå
Disputation
2009-04-24, Betula, Norrlands universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2009-04-06 Skapad: 2009-04-01 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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Olofsson, Eva MariaMarklund, Stefan LBehndig, Anders

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Clinical and Experimental Ophthalmology
Oftalmologi

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