title: 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.affiliation: Department of Pathology, University of Washington School of Medicine, Box 3557470, University of Washington, Seattle, WA 98195-7470, USA. normwolf@u.washington.edu
authors.forename: Norman
authors.initials: N
authors.lastname: Wolf
authors.forename: Philip
authors.initials: P
authors.lastname: Penn
authors.forename: William
authors.initials: W
authors.lastname: Pendergrass
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.forename: Peter
authors.initials: P
authors.lastname: Rabinovitch
authors.forename: George M
authors.initials: GM
authors.lastname: Martin
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000502:physiology; D002386:Cataract / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D011986:Receptors, Somatotropin / Q000235:genetics / Q000502:physiology; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology; D014162:Transfection; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
chemical_list: D002374:Catalase; D005979:Glutathione Peroxidase; D011986:Receptors, Somatotropin; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C000722068:Gpx1 protein, mouse