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      Characterization of the biological antioxidant potential in the vitreous fluid from patients with rhegmatogenous retinal detachment

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          Abstract

          Editor, Oxidative stress has been reported to cause cellular damage and play a role in triggering programmed cell death. In many vitreoretinal disorders, including proliferative diabetic retinopathy (PDR) (Yokoi et al. 2007), age‐related macular degeneration (Rattner & Nathans 2006) and retinitis pigmentosa (Berson 1996), oxidative stress has been implicated in the development of retinal cellular damages (Carmody et al. 1999). Cederlund et al. (2013) previously reported an elevated vitreous level of oxidative stress biomarkers in their small group of patients with rhegmatogenous retinal detachment (RRD), in addition to showing that oxidative stress was related to the RRD severity. Research has also shown that antioxidant treatments can reduce photoreceptor cell death in experimental retinal detachment in animal models (Rostein et al. 2003). The results of these studies indicated that oxidative stress may play an important role in photoreceptor cell death in RRD. Our current study attempted to characterize the biological antioxidant potential (BAP) in the vitreous fluid of RRD by comparing the BAP in the vitreous fluid collected from patients with various vitreoretinal disorders including RRD and then statistically analysing the BAP in relation to the clinical features of RRD. This study was approved by the Institutional Review Board of Hirosaki University Graduate School of Medicine. Undiluted vitreous fluid was obtained at the time of vitrectomy from RRD (n = 45), PDR (n = 93), retinal vein occlusion (RVO, n = 14), epiretinal membrane (ERM, n = 18) and macular hole (MH, n = 24) patients. Biological antioxidant potential (BAP) values were determined by measuring the reducing potential determined by the conversion of Fe3+ to Fe2+ in thiocyanate solution (FREE™, Wismerll, Tokyo). Clinical features of RRD were analysed by examining medical records for the extent of the detachment, duration of symptoms, presence of proliferative vitreoretinopathy (PVR) or vitreous haemorrhage (VH), macular status (on or off), and patient age. Biological antioxidant potential values (μM) were 1860.50 ± 470.50 in RRD, 1647.76 ± 460.53 in PDR, 1863.14 ± 413.76 in RVO, 2169.23 ± 594.01 in ERM and 2258.83 ± 450.79 in MH, respectively. Rhegmatogenous retinal detachment (RRD) exhibited a significantly lower BAP value than MH (anova with post hoc Dunnett's T3 test, p =0.012), while PDR had a significantly smaller BAP than ERM (p = 0.019) and MH (p < 0.001). There were no statistically significant differences in the BAP values between RRD, PDR, RVO and ERM. For the clinical features, BAP values for the detached areas confined within 2 quadrants (2006.59 ± 401.17) were significantly greater than that extended over 3 quadrants (1568.33 ± 474.82, Student's t‐test, p = 0.002). In addition, there was a statistically significant negative correlation between the BAP values and the extent of the detached area, with a Pearson's correlation coefficient of −0.384 (p = 0.008, R1 in Fig. 1). Furthermore, when the BAP values of the MH group were used as the controls (0 quadrant), there was an even stronger correlation, with a Pearson's correlation coefficient of −0.484 (p < 0.001, R2 in Fig. 1). There were no significant correlations noted between BAP and any other features examined. Figure 1 Correlation between BAP and the extent of detachment. BAP is significantly correlated with the extent of the detachment in the RRD group (closed circle, R1 = −0.384, p = 0.008, Pearson's correlation coefficient). When BAP in the MH group is used as the control (= 0 quadrant, open circle), there is a significantly greater correlation between the BAP and the extent of the detachment (R2 = −0.484, p < 0.001). Current results suggest that significantly increased oxidative stress was present in RRD compared to MH. Of the possible clinical features that could influence BAP in RRD, only the extent of the detachment was significantly correlated to the BAP with no significant relationships found for the duration, presence of PVR or VH, macular status and patient age. These results suggest that a detached retina by itself has a much greater influence on intravitreal BAP versus that of the presence of free haemoglobin. Thus, antioxidant treatments may be of benefit in retarding photoreceptor cell death during RRD.

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          Macular degeneration: recent advances and therapeutic opportunities.

          The central retina mediates high acuity vision, and its progressive dysfunction due to macular degeneration is the leading cause of visual disability among adults in industrialized societies. Here, we summarize recent progress in understanding the pathophysiology of macular degeneration and the implications of this new knowledge for treatment and prevention. The past decade has witnessed remarkable advances in this field, including the development of new, non-invasive retinal imaging technologies, the development of animal models for macular disease, and the isolation of many of the genes responsible for both early- and late-onset macular diseases. These advances have set the stage for the development of effective mechanism-based therapies.
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            Protective effect of docosahexaenoic acid on oxidative stress-induced apoptosis of retina photoreceptors.

            In a recent study, it was demonstrated that docosahexaenoic acid (DHA) promotes the survival of retinal photoreceptors in vitro, delaying apoptosis. However, lipid enrichment in DHA is known to contribute to retina vulnerability to oxidative stress. In this study, the effect of oxidative damage on rat retina neurons in vitro and whether DHA enhances or diminishes this damage were investigated. Rat retina neurons in 3-day cultures, with or without DHA, were treated with the oxidant paraquat. After 24 hours, apoptosis, mitochondrial membrane integrity, and Bcl-2 and Bax expression were immunocytochemically determined. Paraquat induced apoptosis in amacrine and photoreceptor neurons, major neuronal types in the culture. Neuronal apoptosis was accompanied by mitochondrial membrane depolarization, an increase in the amount of photoreceptors expressing Bax, and a decrease in those expressing Bcl-2. Addition of DHA reduced photoreceptor apoptosis by almost half, simultaneously preserving their mitochondrial membrane integrity. DHA blocked the paraquat-induced increase in Bax expression and remarkably upregulated Bcl-2 expression. Glia-derived neurotrophic factor, a photoreceptor trophic factor, only slightly increased Bcl-2 expression and did not protect photoreceptors from oxidative damage. Similarly, other fatty acids tested did not prevent photoreceptor apoptosis. These results show that oxidative damage induces apoptosis in retinal neurons during their early development in culture and suggest that the loss of mitochondrial membrane integrity is crucial in the apoptotic death of these cells. DHA activates intracellular mechanisms that prevent this loss and by modulating the levels of pro- and antiapoptotic proteins of the Bcl-2 family selectively protect photoreceptors from oxidative stress.
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              Reactive oxygen species as mediators of photoreceptor apoptosis in vitro.

              Retinitis pigmentosa is a heterogeneous group of retinal degenerations characterized by a progressive loss of photoreceptors through the process of apoptosis. The apoptotic cell death of photoreceptors appears to represent a final common pathway in the pathology of retinitis pigmentosa. Previous studies have reported the ability of antioxidants to ameliorate light-induced retinal degeneration, suggesting a role for oxidative stress in photoreceptor cell death. This study demonstrates an early and sustained increase in intracellular reactive oxygen species accompanied by a rapid depletion of intracellular glutathione in an in vitro model of photoreceptor apoptosis. These early changes in the cellular redox state precede disruption of mitochondrial transmembrane potential, nuclear condensation, DNA nicking, and cell shrinkage, all of which are well-characterized events of apoptotic cell death. The ability of zinc chloride and pyrrolidine dithiocarbamate, two established antioxidants, to inhibit photoreceptor apoptosis through the scavenging of intracellular reactive oxygen species establishes a role for reactive oxygen species as possible mediators of in vitro photoreceptor apoptosis. This study provides a molecular basis for the inhibition of photoreceptor apoptosis by antioxidants. Copyright 1999 Academic Press.
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                Author and article information

                Contributors
                mitsuru@hirosaki-u.ac.jp
                Journal
                Acta Ophthalmol
                Acta Ophthalmol
                10.1111/(ISSN)1755-3768
                AOS
                Acta Ophthalmologica
                John Wiley and Sons Inc. (Hoboken )
                1755-375X
                1755-3768
                24 March 2016
                September 2016
                : 94
                : 6 ( doiID: 10.1111/aos.2016.94.issue-6 )
                : e515-e516
                Affiliations
                [ 1 ] Department of OphthalmologyHirosaki University Graduate School of Medicine HirosakiJapan
                Author notes
                [*] [* ] Correspondence:

                Mitsuru Nakazawa, MD, PhD

                Department of Ophthalmology

                Hirosaki University Graduate School of Medicine, 5 Zaifu‐cho

                Hirosaki 036‐8562, Japan

                Tel: +81 172 39 5094

                Fax: +81 172 37 5735

                Email: mitsuru@ 123456hirosaki-u.ac.jp

                Article
                AOS13002
                10.1111/aos.13002
                5071729
                27008980
                5375a660-591d-42ea-96fc-f83f6ba12ec0
                © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation .

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Page count
                Figures: 1, Tables: 0, Pages: 1, Words: 898
                Funding
                Funded by: Alcon Japan
                Funded by: Santen Pharmaceuticals
                Funded by: K‐Vision
                Categories
                Letter to the Editor
                Letters to the Editor
                Custom metadata
                2.0
                aos13002
                September 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.5 mode:remove_FC converted:20.10.2016

                Ophthalmology & Optometry
                Ophthalmology & Optometry

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