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N.S. Wolf, W. Pendergrass, P. Penn, H. Van Remmen, A. Bartke; Cataract Incidence and Severity Compared to LEC Mitochondrial Function in Aging and Oxidative Control–Affected Mutant Mice . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2658.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the stages of cataract development and mitochondrial status in lenses of young (5–7 months) and old (21–25 months) C57BL/6 mice, either normal or with either one of two mutations potentially affecting mitochondrial function. Methods: Grading of lens opacities was done on the same subjects by hand–held slit lamp for living animals and on their freshly removed lenses viewed under a dissecting scope, with similar results. The following LEC and whole lens measurements were made by confocal microscopy: 1) LEC mitochondrial membrane potential (MMP) by CMX rosamine, with protein mass control by Mitotracker green uptake, 2) lens peroxide production by dichlorofluorosine (DCF); 3) O2 utilization by reduced rosamine; 4) DNA retention by Hoechst dye. Results: 1) Lens opacities progressed with age in both normal and in the below–noted mutant mice, 2) In all old mice there was reduced LEC utilization of O2, as well as increased lens peroxide content; 3) In all old mice there was retention of DNA in and around nuclear and mitochondrial remnants in deeply internalized fiber cells, this was localized at the sites of peroxide presence and lens opacity; 4) lenses of old glutathione peroxidase–1 homozygous knockout mice (GPX–1 KO) had more severe cataracts and greater reduction of O2 utilization than same age controls; 5) in long–lived dwarf (GHRKO) mice with non–functional growth hormone receptors and almost no circulating IGF–1 there was both a delay in age–related cataract formation and reduced MMP in the young mutant versus normals. Conclusions: Pigmented normal mice have progressive lens opacities and develop cataracts in all old animals that we have examined (N.Wolf et al. 2000, N. Wolf and P. Penn, 2001). LEC MMP, O2 utiliszation and peroxide production were altered with age as noted above. Peroxides and inappropriate DNA collections localized at cataract sites.. Lack of GPX–1 increases severity of cataract, while lower/absent serum IGF–1 is protective. Our findings suggest associated causes and mechanisms of age–related cataract development.
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