Age-related cataract progression in five mouse models for anti-oxidant protection or hormonal influence.

Abstract

Five mouse models with known alterations of resistance to oxidative damage were compared by slit lamp examination for the presence and degree of advancement of age-related cataract in young adult and old animals along with wild type controls. A group of young and old normal C57BL/6Jax mice were examined first to constitute a standard, and they were found to exhibit age-related cataract development. Following this, four models on the C57BL/6 background with imposed genetic alterations affecting anti-oxidant enzyme presence or activity, and one outbred model in which a deletion blocked the growth hormone/IGF-1 axis, were similarly examined. There was no evidence of foetal or juvenile cataract development in any of these models, and an age-related severity for lens opacities was shown between young adult and old mice in all groups. Model 1, mice null for the anti-oxidant gene glutathione peroxidase-1 (GPX1) had significantly advanced cataracts in older mice vs. same age controls. In mouse model 2 hemizygous knockout of SOD2 (MnSOD) did not affect age-related cataract development. In model 3 combining the GPX1 and SOD2 deficiencies in the same animal did not advance cataract development beyond that of the GPX1 null alone. In model 4 the addition of anti-oxidant protection in the lens by transfection of human catalase targeted only to the mitochondria resulted in a significant delay in cataract development. The 5th model, growth hormone receptor knockout (GHR-/-) mice, also demonstrated a significant reduction in age-related cataract development, as well as dwarfism. These findings, in general, support the oxidative theory of age-related cataract development. The exception, the partial deletion of SOD2 in the hemizygous KO model, probably did not represent a sufficiently severe deprivation of anti-oxidant protection to produce pathologic changes in the lens.

• Authors: Norman Wolf, Philip Penn, William Pendergrass, Holly Van Remmen, Andrzej Bartke, Peter Rabinovitch, George M Martin
• Journal: Experimental eye research (Exp Eye Res) Vol. 81 Issue 3 Pg. 276-85 (Sep 2005) ISSN: 0014-4835 [Print] England
• PMID: 16129095 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Somatotropin
• Catalase
• Glutathione Peroxidase
• Superoxide Dismutase
• superoxide dismutase 2
• Glutathione Peroxidase GPX1
• Gpx1 protein, mouse

Topics

• Aging (pathology, physiology)
• Animals
• Catalase (genetics, physiology)
• Cataract (genetics, pathology, physiopathology, prevention & control)
• Disease Models, Animal
• Disease Progression
• Female
• Glutathione Peroxidase (genetics, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oxidative Stress
• Receptors, Somatotropin (genetics, physiology)
• Superoxide Dismutase (genetics, physiology)
• Transfection
• Glutathione Peroxidase GPX1