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      Photoperiodic regime influences onset of lens opacities in a non-human primate

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          Abstract

          Background

          Opacities of the lens are typical age-related phenomena which have a high influence on photoreception and consequently circadian rhythm. In mouse lemurs, a small bodied non-human primate, a high incidence (more than 50% when >seven years) of cataracts has been previously described during aging. Previous studies showed that photoperiodically induced accelerated annual rhythms alter some of mouse lemurs’ life history traits. Whether a modification of photoperiod also affects the onset of age dependent lens opacities has not been investigated so far. The aim of this study was therefore to characterise the type of opacity and the mouse lemurs’ age at its onset in two colonies with different photoperiodic regimen.

          Methods

          Two of the largest mouse lemur colonies in Europe were investigated: Colony 1 having a natural annual photoperiodic regime and Colony 2 with an induced accelerated annual cycle. A slit-lamp was used to determine opacities in the lens. Furthermore, a subset of all animals which showed no opacities in the lens nucleus in the first examination but developed first changes in the following examination were further examined to estimate the age at onset of opacities. In total, 387 animals were examined and 57 represented the subset for age at onset estimation.

          Results

          The first and most commonly observable opacity in the lens was nuclear sclerosis. Mouse lemurs from Colony 1 showed a delayed onset of nuclear sclerosis compared to mouse lemurs from Colony 2 (4.35 ± 1.50 years vs. 2.75 ± 0.99 years). For colony 1, the chronological age was equivalent to the number of seasonal cycles experienced by the mouse lemurs. For colony 2, in which seasonal cycles were accelerated by a factor of 1.5, mouse lemurs had experienced 4.13 ± 1.50 seasonal cycles in 2.75 ± 0.99 chronological years.

          Discussion

          Our study showed clear differences in age at the onset of nuclear sclerosis formation between lemurs kept under different photoperiodic regimes. Instead of measuring the chronological age, the number of seasonal cycles ( N = four) experienced by a mouse lemur can be used to estimate the risk of beginning nuclear sclerosis formation. Ophthalmological examinations should be taken into account when animals older than 5–6 seasonal cycles are used for experiments in which unrestricted visual ability has to be ensured. This study is the first to assess and demonstrate the influence of annual photoperiod regime on the incidence of lens opacities in a non-human primate.

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          Most cited references55

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          Age-related nuclear cataract-oxidation is the key.

          Age is by far the biggest risk factor for cataract, and it is sometimes assumed that cataract is simply an amplification of this aging process. This appears not to be the case, since the lens changes associated with aging and cataract are distinct. Oxidation is the hallmark of age-related nuclear (ARN) cataract. Loss of protein sulfhydryl groups, and the oxidation of methionine residues, are progressive and increase as the cataract worsens until >90% of cysteine and half the methionine residues are oxidised in the most advanced form. By contrast, there may be no significant oxidation of proteins in the centre of the lens with advancing age, even past age 80. The key factor in preventing oxidation seems to be the concentration of nuclear glutathione (GSH). Provided that nuclear GSH levels can be maintained above 2 mm, it appears that significant protein oxidation and posttranslational modification by reactive small molecules, such as ascorbate or UV filter degradation products, is not observed. Adequate coupling of the metabolically-active cortex, the source of antioxidants such as GSH, to the quiescent nucleus, is crucial especially since it would appear that the cortex remains viable in old lenses, and even possibly in ARN cataract lenses. Therefore it is vital to understand the reason for the onset of the lens barrier. This barrier, which becomes apparent in middle age, acts to impede the flow of small molecules between the cortex and the nucleus. The barrier, rather than nuclear compaction (which is not observed in human lenses), may contribute to the lowered concentration of GSH in the lens nucleus after middle age. By extending the residence time within the lens centre, the barrier also facilitates the decomposition of intrinsically unstable metabolites and may exacerbate the formation of H(2)O(2) in the nucleus. This hypothesis, which is based on the generation of reactive oxygen species and reactive molecules within the nucleus itself, shifts the focus away from theories for cataract that postulated a primary role for oxidants generated outside of the lens. Unfortunately, due to marked variability in the lenses of different species, there appears at present to be no ideal animal model system for studying human ARN cataract.
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            Circadian photoreception: ageing and the eye’s important role in systemic health

            Aim: To analyse how age-related losses in crystalline lens transmittance and pupillary area affect circadian photoreception and compare the circadian performance of phakic and pseudophakic individuals of the same age. Methods: The spectral sensitivity of circadian photoreception peaks in the blue part of the spectrum at approximately 460 nm. Photosensitive retinal ganglion cells send unconscious information about environmental illumination to non-visual brain centres including the human body’s master biological clock in the suprachiasmatic nuclei. This information permits human physiology to be optimised and aligned with geophysical day–night cycles using neural and hormonal messengers including melatonin. Age-related transmittance spectra of crystalline lenses and photopic pupil diameter are used with the spectral sensitivity of melatonin suppression and the transmittance spectra of intraocular lenses (IOLs) to analyse how ageing and IOL chromophores affect circadian photoreception. Results: Ageing increases crystalline lens light absorption and decreases pupil area resulting in progressive loss of circadian photoreception. A 10-year-old child has circadian photoreception 10-fold greater than a 95-year-old phakic adult. A 45-year-old adult retains only half the circadian photoreception of early youth. Pseudophakia improves circadian photoreception at all ages, particularly with UV-only blocking IOLs which transmit blue wavelengths optimal for non-visual photoreception. Conclusions: Non-visual retinal ganglion photoreceptor responses to bright, properly timed light exposures help assure effective circadian photoentrainment and optimal diurnal physiological processes. Circadian photoreception can persist in visually blind individuals if retinal ganglion cell photoreceptors and their suprachiasmatic connections are intact. Retinal illumination decreases with ageing due to pupillary miosis and reduced crystalline lens light transmission especially of short wavelengths. Inadequate environmental light and/or ganglion photoreception can cause circadian disruption, increasing the risk of insomnia, depression, numerous systemic disorders and possibly early mortality. Artificial lighting is dimmer and less blue-weighted than natural daylight, contributing to age-related losses in unconscious circadian photoreception. Optimal intraocular lens design should consider the spectral requirements of both conscious and unconscious retinal photoreception.
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              Oxidative stress in cataracts.

              Joe Vinson (2006)
              Oxidative stress is the result of an imbalance of antioxidants and pro-oxidants. Since toxic free radicals are the result of normal metabolism, their destruction is imperative. Cataracts are the leading cause of blindness worldwide. Opacity of the lens is a direct result of oxidative stress. Cataracts occur primarily due to age, but also are common in diabetes where superoxide in the mitochondria is elevated as a result of hyperglycemia. This review will investigate the risk factors of cataract including diet (vitamins, fat and alcohol) as well as UV light and diabetes. The pathophysiology of lens opacification will be discussed and related to the biochemistry, especially during the aging process and in diabetes. Animal and human supplemental antioxidant studies will be reviewed and the mechanisms discussed for cataract prevention and treatment. New genetic engineering approaches to overexpress antioxidant enzymes have given intriguing results and show promise. Lastly, a new approach to target mitochondrial superoxide with antioxidant molecules will be outlined.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                peerj
                PeerJ
                PeerJ Inc. (San Francisco, USA )
                2167-8359
                4 May 2017
                2017
                : 5
                : e3258
                Affiliations
                [1 ]Institute of Zoology, Tierärztliche Hochschule Hannover , Hanover, Lower Saxony, Germany
                [2 ]Clinic for Small Animals, Tierärztliche Hochschule Hannover , Hanover, Lower Saxony, Germany
                [3 ]Department of Molecular Mechanisms in Neurodegenerative Diseases Inserm U1198, Univ. Montpellier , Montpellier, France
                [4 ]Centre for Comparative and Evolutionary Psychology, University of Portsmouth , Portsmouth, United Kingdom
                Article
                3258
                10.7717/peerj.3258
                5420196
                28484672
                ba38999c-95ae-4027-8751-bebda834ac4c
                ©2017 Dubicanac et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 9 January 2017
                : 30 March 2017
                Funding
                Funded by: European Community’s 7th Framework Program
                Award ID: FP7/2007-2013
                Funded by: “DEVELAGE”
                Award ID: 278486
                Funded by: DAAD PROCOPE
                Award ID: 55924926
                This study was partly supported by the European Community’s 7th Framework Program (FP7/2007-2013) under grant agreement no. 278486 acronym “DEVELAGE” (EZ, JMV) and a DAAD PROCOPE Grant No. 55924926 (MJ). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Veterinary Medicine
                Ophthalmology

                nuclear sclerosis,aging,photoperiod,mouse lemur,cataract,primate

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