scholarly journals Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

2020 ◽  
Vol 21 (15) ◽  
pp. 5182
Author(s):  
Darya V. Telegina ◽  
Elizabeth A. Kulikova ◽  
Oyuna S. Kozhevnikova ◽  
Alexander V. Kulikov ◽  
Tatyana M. Khomenko ◽  
...  

Tyrosine phosphatase STEP (striatal-enriched tyrosine protein phosphatase) is a brain-specific protein phosphatase and is involved in the pathogenesis of many neurodegenerative diseases. Here, we examined the impact of STEP on the development of age-related macular degeneration (AMD)-like pathology in senescence-accelerated OXYS rats. Using OXYS and Wistar rats (control), we for the first time demonstrated age-dependent changes in Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the retina. The increases in STEP protein levels and the decrease of total and STEP phosphatase activities in the retina (as compared with Wistar rats) preceded the manifestation of clinical signs of AMD in OXYS rats (age 20 days). There were no differences in these retinal parameters between 13-month-old Wistar rats and OXYS rats with pronounced signs of AMD. Inhibition of STEP with TC-2153 during progressive AMD-like retinopathy (from 9 to 13 months of age) reduced the thickness of the retinal inner nuclear layer, as evidenced by a decreased amount of parvalbumin-positive amacrine neurons. Prolonged treatment with TC-2153 had no effect on Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the OXYS retina. Thus, TC-2153 may negatively affect the retina through mechanisms unrelated to STEP.

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
M. L. Perepechaeva ◽  
A. Yu. Grishanova ◽  
E. A. Rudnitskaya ◽  
N. G. Kolosova

The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD). The aim of this work was to test whether SkQ1 affects transcriptional activity ofAhR(aryl hydrocarbon receptor) andNrf2(nuclear factor erythroid 2-related factor 2), which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that onlyAhRandAhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased theAhRmRNA level in both OXYS and Wistar rats. At baseline, the retinalCyp1a1mRNA level was lower in OXYS rats. SkQ1 supplementation decreased theCyp1a1mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. BaselineCyp1a2andCyp1b1mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain,Cyp1a2andCyp1b1mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.


2007 ◽  
Vol 292 (4) ◽  
pp. F1215-F1218 ◽  
Author(s):  
Gloria Rashid ◽  
Jacques Bernheim ◽  
Janice Green ◽  
Sydney Benchetrit

Parathyroid hormone (PTH), the major systemic calcium-regulating hormone, has been linked to uremic vascular changes. Considering the possible deleterious action of PTH on vascular structures, it seemed logical to evaluate the impact of PTH on the receptor of advanced glycation end products (RAGE) and interleukin 6 (IL-6) mRNA and protein expression, taking into account that such parameters might be involved in the pathogenesis of vascular calcification, atherosclerosis, and/or arteriolosclerosis. Human umbilical vein cord endothelial cells (HUVEC) were stimulated for 24 h with 10−12–10−10 mol/l PTH. The mRNA expression of RAGE and IL-6 was established by reverse transcriptase/PCR techniques. RAGE protein levels were determined by Western blot and IL-6 secretion was measured by ELISA. The pathways by which PTH may have an effect on HUVEC functions were evaluated. PTH (10−11–10−10mol/l) significantly increased RAGE mRNA and protein expression. PTH also significantly increased IL-6 mRNA expression without changes at protein levels. The addition of protein kinase (PKC or PKA) inhibitors or nitric oxide (NO) synthase inhibitors significantly reduced the RAGE and IL-6 mRNA expression and the RAGE protein expression. PTH stimulates the mRNA expressions of RAGE and IL-6 and the protein expression of RAGE. These stimulatory effects are probably through PKC and PKA pathways and are also NO dependent. Such data may explain the possible impact of PTH on the atherosclerotic and arteriosclerotic progression.


2021 ◽  
pp. bjophthalmol-2021-319383
Author(s):  
Susan P Mollan ◽  
Dun Jack Fu ◽  
Ching-Yi Chuo ◽  
Jacqueline G Gannon ◽  
Wen Hwa Lee ◽  
...  

ObjectivePredicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.Methods and analysisThis retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).ResultsAt our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%–7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%–7.8%) after 12 months without treatment.ConclusionsHere, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.Trial registration numberNCT00056836.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Barbara Pereira da Silva ◽  
Marcella Duarte Villas Mishima ◽  
Renata Celi Lopes Toledo ◽  
Maria Eliza de Castro Moreira ◽  
Neuza Costa ◽  
...  

Abstract Objectives The objective is to investigate the influence of chia consumption on inflammation, oxidative stress, and blood lipid profile in adult female ovariectomized Wistar rats fed high-fat diet Methods Forty ovariectomized and 40 intact (SHAM) rats were allocated into 8 groups (n = 10), and received one of the following four diets: standard diet (ST); standard diet + chia (STC); high-fat diet (HF); high-fat diet + chia (HFC) during 126 days. Biochemical parameters and biomarkers of lipid peroxidation, inflammation, and oxidative stress were evaluated. The mRNA expression of proteins involved in inflammation such as PPAR-α, NFκB, TNF-α and Zn-SOD1 were analyzed, as well as TNF-α and IL-1β levels. The results were subjected to ANOVA at 5% probability. Post hoc Duncan test was carried out to compare means among the groups. Test-t was used to compare the same diet group with ovariectomy or not. Results Chia intake increased HDL-c and reduced LDL-c levels. Among the ovariectomized groups, the animals fed chia showed higher SOD mRNA expression and activity. The consumption of the HF did not alter the total antioxidant capacity. In addition, chia consumption did not improve this parameter. Nevertheless, plasma catalase concentration was higher in STC group. MDA concentration was higher in all groups fed HF. PPAR-α mRNA expression was higher in the STC group. Besides, high fat diet consumption was able to reduce the PPAR-α mRNA expression. The NFκB mRNA expression were lower in STC groups. However, mRNA expression and the protein levels of TNF-α were lower in the rats fed standard diet. Nevertheless, the protein levels of IL-1β were lower in the rats fed standard diet and high fat diet with chia. Conclusions In general, ovariectomy did not influence inflammatory and oxidative stress parameters. Chia intake during 126 days was able to improve antioxidant activity, increasing SOD expression, PPAR-α expression, catalase concentration, and HDL-c levels in adults female rats submitted or not to ovariectomy and fed a standard or a high-fat diet. In addition, chia consumption decrease inflammatory markes, IL-1β and LDL-c concentration. Funding Sources Foundation for Research Support of Minas Gerais (FAPEMIG, Brazil); Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil), and the National Counsel of Technological and Scientific Development (CNPq, Brazil). Supporting Tables, Images and/or Graphs


2014 ◽  
Vol 1 (1) ◽  
pp. 36 ◽  
Author(s):  
Siti Fatimah ◽  
Muji Rahayu ◽  
Siti Aminah

Background : Egg  is one of the animal protein source, which has delicious taste, easy to digest and highly nutritious. Besides its affordable price, its supply availability is unquestionable as well. However, due to its short storability, it requires special treatment, such as preserving, to store it for long period. One way to preserve the egg is by pickling egg, which generally requires seven to ten days of marinating. During the process of marinating, there will be a visual change of egg white and yolk. Their structures  will be more solid (the occurrence of thickening process) because salinization will lead to protein denaturalization. Consequently, it has an influence as well towards the content of egg white protein of duck egg. This study is aimed to explore the impact of various time of pickling egg towards egg white protein of duck egg. Method  : The study where takes place in a laboratories, is a true experimental study for the reason that the researcher must provide intervention, hence all of potentially confounding variables are manageable. Samples that had been used in this study are duck eggs which were bought from North Brebes. This study is expected to generate data from four various time of pickling egg and control (no treatment). Since there are four samples, accordingly the number of data resulted are twenty. The resulted data will be descriptively presented in table, graph, presentation, and narration. Result  : Protein level examination within duck white egg shows changes  in protein levels that occurs in every variation of pickling egg time, where the average results of the assay of duck egg white protein is 14.94% without treatment (control), in five days of pickling time is 13.68%, in seven days of pickling time is 13.29%, in nine days of pickling time is 12.87% and eleven days of pickling time is 12.78%. Conclusion  : There is a significant impact among the period of pickling time to the protein level degradation of duck white egg. Keywords : Duck egg, period of pickling time, level protein of duck white egg.


2020 ◽  
Vol 6 (6) ◽  
pp. 94-100
Author(s):  
Serge-Olivier Konan KOUASSI ◽  
◽  
Yves Bénarèce Tra DJE BI ◽  
Soualio KAMAGATE ◽  
Mathieu Nahounou BLEYERE ◽  
...  

The study aims to determine the impact of dietary crude protein levels on the hematological parameters of Japanese quail from growth to ovipositor. To this end, five feeds with different crude protein levels (18, 20, 22, 24 and 26%) were supplied to 700 quails of three weeks of age. These were subdivided into six batches, including three batches of females and three batches of males for each feed group. After subjecting the quails to diets containing the different protein levels, four samples were taken at the fourth, fifth, sixth and seventh week of age. The samples taken were analyzed using an SYSMEX XN 350 automated hematological analyzer. The results of this investigation indicated that non-significant differences (P > 0.05) were observed in hematological parameters in both female and male quails. This study showed that dietary crude protein levels had no impact on the health status of Japanese quails. Keywords: Japanese quails, Crude protein, Hematological parameters.


2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.


2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elżbieta Krytkowska ◽  
Aleksandra Grabowicz ◽  
Katarzyna Mozolewska-Piotrowska ◽  
Zofia Ulańczyk ◽  
Krzysztof Safranow ◽  
...  

AbstractDisturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β =  + 0.18, p = 0.0007, β =  + 0.18, p = 0.0008, respectively) and to dry AMD (β =  + 0.17, p = 0.00003 for both ATC and AVC and β =  − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs =  − 0.13, p < 0.05; Rs =  − 0.12; p < 0.05, Rs =  − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs =  − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.


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