Defective superoxide-dismutase molecules accumulate with age in human lenses

ArticleinAlbrecht von Graæes Archiv für Ophthalmologie 225(2):133-6 · February 1987with301 Reads
DOI: 10.1007/BF02160345 · Source: PubMed
The specific activity of superoxide dismutase (SOD) in human transparent lenses declines as a function of age. Immunotitration using monospecific antibodies showed that, with increasing age, lenses exhibit an accumulation of catalytically inactive, but antigenically reactive, enzyme molecules. Antiserum produced against denatured enzyme removed the inactive molecules from the lens homogenates without affecting the enzyme activity. These aberrant molecules are at least partially denatured and are totally devoid of catalytic activity.
    • "The majority of mature LFCs, including those at the lens nucleus, no longer actively support these ATP-sapping activities [8,[51][52][53]. Furthermore, metabolism in the nuclear LFCs is minimal [54][55][56][57], defining another physiological metabolic state that is significantly depressed. An active circulation system connecting the lens cortex to the lens nucleus carries ions and metabolites to supply and sustain the mature LFCs with nutrients and also controls the volume of these cells [58]. "
    [Show abstract] [Hide abstract] ABSTRACT: The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The recent recommendations of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens have now been adopted in the European Union and are under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2 Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effect of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection.
    Article · Jul 2016 · Age
    • "Lens cells have abundant antioxidant enzymes [172], even if the lens appears to be exposed to relatively low levels of oxygen and its cells have no mitochondria, which are the main endogenous source of ROS. The antioxidant systems of the lens include SOD [173] and glutathione peroxidase [174], and endogenous free radical scavengers such as ascorbic acid and GSH [175]. Catalase, which catalyzes the decomposition of hydrogen peroxide into water and oxygen and prevents cell damage from high levels of ROS, seems to have little importance in cataract pathogenesis [176]. "
    [Show abstract] [Hide abstract] ABSTRACT: The human eye is constantly exposed to sunlight and artificial lighting. Exogenous sources of reactive oxygen species (ROS) such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins contribute to oxidative damage in ocular tissues. Long-term exposure to these insults places the aging eye at considerable risk for pathological consequences of oxidative stress. Furthermore, in eye tissues, mitochondria are an important endogenous source of ROS. Over time, all ocular structures, from the tear film to the retina, undergo oxidative stress, and therefore, the antioxidant defenses of each tissue assume the role of a safeguard against degenerative ocular pathologies. The ocular surface and cornea protect the other ocular tissues and are significantly exposed to oxidative stress of environmental origin. Overwhelming of antioxidant defenses in these tissues clinically manifests as pathologies including pterygium, corneal dystrophies, and endothelial Fuch's dystrophy. The crystalline lens is highly susceptible to oxidative damage in aging because its cells and their intracellular proteins are not turned over or replaced, thus providing the basis for cataractogenesis. The trabecular meshwork, which is the anterior chamber tissue devoted to aqueous humor drainage, has a particular susceptibility to mitochondrial oxidative injury that affects its endothelium and leads to an intraocular pressure increase that marks the beginning of glaucoma. Photo-oxidative stress can cause acute or chronic retinal damage. The pathogenesis of age-related macular degeneration involves oxidative stress and death of the retinal pigment epithelium followed by death of the overlying photoreceptors. Accordingly, converging evidence indicates that mutagenic mechanisms of environmental and endogenous sources play a fundamental pathogenic role in degenerative eye diseases.
    Full-text · Article · Jan 2013
    • "The pronounced changes with age are unlikely to be due to the activity of lens enzymes. Although phospholipase activity has been observed in the whole lens, even at 60 years of age (Kamei 1996), several separate studies indicate that metabolic pathways are absent from the centre of adult human lenses (Dovrat and Gershon 1981; Dovrat et al. 1984; Scharf et al. 1987; Zhu et al. 2010b). Fiber cells in the lens nucleus lack organelles and, since there is no protein turnover (Lynnerup et al. 2008), it is likely that the enzymes which were active in the centre of young lenses have been denatured due to decades of exposure to body temperature. "
    [Show abstract] [Hide abstract] ABSTRACT: The human lens nucleus is formed in utero, and from birth onwards, there appears to be no significant turnover of intracellular proteins or membrane components. Since, in adults, this region also lacks active enzymes, it offers the opportunity to examine the intrinsic stability of macromolecules under physiological conditions. Fifty seven human lenses, ranging in age from 12 to 82 years, were dissected into nucleus and cortex, and the nuclear lipids analyzed by electrospray ionization tandem mass spectrometry. In the first four decades of life, glycerophospholipids (with the exception of lysophosphatidylethanolamines) declined rapidly, such that by age 40, their content became negligible. In contrast the level of ceramides and dihydroceramides, which were undetectable prior to age 30, increased approximately 100-fold. The concentration of sphingomyelins and dihydrosphingomyelins remained unchanged over the whole life span. As a consequence of this marked alteration in composition, the properties of fiber cell membranes in the centre of young lenses are likely to be very different from those in older lenses. Interestingly, the identification of age 40 years as a time of transition in the lipid composition of the nucleus coincides with previously reported macroscopic changes in lens properties (e.g., a massive age-related increase in lens stiffness) and related pathologies such as presbyopia. The underlying reasons for the dramatic change in the lipid profile of the human lens with age are not known, but are most likely linked to the stability of some membrane lipids in a physiological environment.
    Full-text · Article · Sep 2011
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