scholarly journals Diacron reactive oxygen metabolites and biological antioxidant potential tests for patients with age-related macular degeneration

2019 ◽  
Author(s):  
Toshiyuki Matsuura ◽  
Hiroki Kaneko ◽  
Kei Takayama ◽  
Rei Shibata ◽  
Keiko Kataoka ◽  
...  

Abstract Background: Previously, we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests are known markers of oxidative stress.The Aims of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stress in patients with nAMD. Methods: Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9 ± 14.0 years; 10 men), and d-ROMs and BAP tests were examined. Results: In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P < .05). There was a significant correlation between d-ROM level and CNV lesion area in the male nAMD group (r =.42, P = .05). There were no significant differences in mean BAP test results between the nAMD patients and controls for either sex (men: 2241 ± 549 vs. 2136 ± 246 μmol/L; women: 2263 ± 292 vs. 2335 ± 161 μmol/L). For the male subjects, serum d-ROM levels were significantly higher in nAMD patients than in control subjects and d-ROM levels were significantly correlated with CNV area. Conclusion: The d-ROMs test may provide a useful indicator of nAMD in men but not in women.

2019 ◽  
Author(s):  
Toshiyuki Matsuura ◽  
Hiroki Kaneko ◽  
Kei Takayama ◽  
Rei Shibata ◽  
Keiko Kataoka ◽  
...  

Abstract Background : Previously,we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites(d-ROMs) andbiologicalantioxidant potential (BAP) tests are known markers ofoxidative stress. The aim of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stressin patients with nAMD. Methods : Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9± 14.0 years; 10 men), and d-ROMs and BAP tests were examined. Results : In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P < .05). There was a significant correlation between d-ROM level and CNV lesion area in the male nAMD group (r =.42, P = .05). There were no significant differences in mean BAP test results between the nAMD patients and controls for either sex (men: 2241 ± 549 vs. 2136 ± 246 μmol/L; women: 2263 ± 292 vs. 2335 ± 161 μmol/L). Conclusion : The d-ROMs test may provide a useful indicator of nAMD in men but not in women.


PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0233550
Author(s):  
Masahito Morimoto ◽  
Toshiaki Hashimoto ◽  
Yoshimi Tsuda ◽  
Tadanori Nakatsu ◽  
Taisuke Kitaoka ◽  
...  

2004 ◽  
Vol 19 (3) ◽  
pp. 250-253 ◽  
Author(s):  
A. Cavalleri ◽  
C. Colombo ◽  
E. Venturelli ◽  
R. Miceli ◽  
L. Mariani ◽  
...  

2012 ◽  
Vol 90 (5) ◽  
pp. e399-e403 ◽  
Author(s):  
Semira Kaya ◽  
Günther Weigert ◽  
Berthold Pemp ◽  
Stefan Sacu ◽  
René Marcel Werkmeister ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Sarah de Jong ◽  
Anita de Breuk ◽  
Bjorn Bakker ◽  
Suresh Katti ◽  
Carel B. Hoyng ◽  
...  

Complement factor I (FI) is a central inhibitor of the complement system, and impaired FI function increases complement activation, contributing to diseases such as age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (aHUS). Genetic variation in complement factor I (CFI) has been identified in both AMD and aHUS, with more than half of these variants leading to reduced FI secretion levels. For many of the variants with normal FI secretion, however, functional implications are not yet known. Here we studied 11 rare missense variants, with FI secretion levels comparable to wildtype, but a predicted damaging effects based on the Combined Annotation Dependent Depletion (CADD) score. Three variants (p.Pro50Ala, p.Arg339Gln, and p.Ser570Thr) were analyzed in plasma and serum samples of carriers affected by AMD. All 11 variants (nine for the first time in this study) were recombinantly expressed and the ability to degrade C3b was studied with the C3b degradation assay. The amount of degradation was determined by measuring the degradation product iC3b with ELISA. Eight of 11 (73%) mutant proteins (p.Pro50Ala, p.Arg339Gln, p.Ile340Thr, p.Gly342Glu, p.Gly349Arg, p.Arg474Gln, p.Gly487Cys, and p.Gly512Ser) showed significantly impaired C3b degradation, and were therefore classified as likely pathogenic. Our data indicate that genetic variants in CFI with a CADD score &gt;20 are likely to affect FI function, and that monitoring iC3b in a degradation assay is a useful tool to establish the pathogenicity of CFI variants in functional studies.


2020 ◽  
Vol 9 (7) ◽  
pp. 2293
Author(s):  
Ahmed S. Ibrahim ◽  
Khaled Hussein ◽  
Fang Wang ◽  
Ming Wan ◽  
Nancy Saad ◽  
...  

Disruption of retinal pigment epithelial (RPE) barrier integrity and RPE migration are hallmark features in neovascular age-related macular degeneration (nAMD), but the underlying causes and pathophysiology are not completely well-defined. Herein, we aimed to evaluate the effect of bone morphogenetic proteins (BMPs) on the barrier function and migration of RPE. In particular, we investigated the role of BMP2 and BMP4 in these processes as our analysis of RNA-sequencing (seq) data from human donor eyes demonstrated that they are highly differentially expressed BMP members in macular RPE/choroid versus macular retina. We used electrical cell-substrate impedance sensing (ECIS) system to monitor precisely in real time the barrier integrity and migration of ARPE-19 after treatment with various concentrations of BMP2 or BMP4. Immunofluorescence was also used to assess the changes in the expression and the organization of the key tight junction protein, zona occludens (ZO)-1, in ARPE-19 cells under BMP2 or BMP4 treatment. This was followed by measuring the activity of matrix metalloproteinases (MMPs). Finally, RNA-seq and ELISA were used to determine the local and circulating levels of BMP2 and BMP4 in retinas and serum samples from nAMD donors. Our ECIS results showed that BMP4 but not BMP2 decreased the transcellular electrical resistance (TER) of ARPE-19 and increased their migration in comparison with control (vehicle-treated cells). Furthermore, immunofluorescence showed a disorganization of ZO-1 in BMP4-treated ARPE-19 not in BMP2-treated cells or vehicle-treated controls. This effect of BMP4 was associated with significant increases in the activity of MMPs, specifically MMP2. Lastly, these results were corroborated by additional findings that circulating but not local BMP4 levels were significantly higher in nAMD donor samples compared to controls. Collectively, our results demonstrated unreported effects of BMP4 on inducing RPE dysfunction and suggest that BMP4 but not BMP2 may represent a potential therapeutic target in nAMD.


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