scholarly journals The Evaluation of oxidative stress, 3-nitrotyrosine, and HMGB-1 levels in patients with Wet Type Age-Related Macular Degeneration

2021 ◽  
Author(s):  
Kürşad Ramazan Zor ◽  
İsmail Sarı ◽  
Gamze Yıldırım ◽  
İnayet Güntürk ◽  
Erkut Küçük ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Age Related ◽  
Significant Difference ◽  
Commercial Kits ◽  
Routine Therapy

Abstract   Background: This study aims to compare serum HMGB-1, 3-nitrotyrosine (3-NT), TAS, TOS, and OSI levels in Wet-type Age-Related Macular Degeneration (wAMD) patients and healthy controls to determine the correlation of these parameters with each other.   Methods: Thirty patients with Wet-type Age-Related Macular Degeneration (wAMD) and 27 healthy adults, as controls were enrolled in the study. We determined the TAS and TOS levels in serum samples of both groups using commercial kits on a microplate reader. Serum HMGB-1 and 3-NT levels were measured with the enzyme-linked immunosorbent assay method.   Results: HMGB-1 levels were significantly higher in the patient group (137.51 pg / mL, p=0.001), while there was no difference between the two groups in serum 3-NT levels (p=0.428). A statistically significant difference found in the levels of TOS and OSI (p=0.001 and p=0.045, respectively) between the patients and controls, however, no significant difference was observed between the groups in terms of TAS levels (p=0.228).   Conclusions: Oxidative stress and HMGB-1 levels were increased in wAMD patients and enhanced oxidative stress may be associated with increased tissue necrosis and inflammation. Thus administration of antioxidant treatment in addition to routine therapy should be considered in wAMD.  

scholarly journals Development of an ultra-sensitive human IL-33 biomarker assay for age-related macular degeneration and asthma drug development

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Elaine Mai ◽  
Joyce Chan ◽  
Levina Goon ◽  
Braeden K. Ego ◽  
Jack Bevers ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Age Related Macular Degeneration ◽  
Reduced Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 33 ◽  
Age Related ◽  
Significant Difference ◽  
High Concentrations

Abstract Background Over the past decade, human Interleukin 33 (hIL-33) has emerged as a key contributor to the pathogenesis of numerous inflammatory diseases. Despite the existence of several commercial hIL-33 assays spanning multiple platform technologies, their ability to provide accurate hIL-33 concentration measurements and to differentiate between active (reduced) and inactive (oxidized) hIL-33 in various matrices remains uncertain. This is especially true for lower sample volumes, matrices with low hIL-33 concentrations, and matrices with elevated levels of soluble Interleukin 1 Receptor-Like 1 (sST2), an inactive form of ST2 that competes with membrane bound ST2 for hIL-33 binding. Results We tested the performance of several commercially available hIL-33 detection assays in various human matrices and found that most of these assays lacked the sensitivity to accurately detect reduced hIL-33 at biologically relevant levels (sub-to-low pg/mL), especially in the presence of human sST2 (hsST2), and/or lacked sufficient target specificity. To address this, we developed and validated a sensitive and specific enzyme-linked immunosorbent assay (ELISA) capable of detecting reduced and total hIL-33 levels even in the presence of high concentrations of sST2. By incorporating the immuno-polymerase chain reaction (iPCR) platform, we further increased the sensitivity of this assay for the reduced form of hIL-33 by ~ 52-fold. Using this hIL-33 iPCR assay, we detected hIL-33 in postmortem human vitreous humor (VH) samples from donors with age-related macular degeneration (AMD) and found significantly increased hIL-33 levels when compared to control individuals. No statistically significant difference was observed in aqueous humor (AH) from AMD donors nor in plasma and nasosorption fluid (NF) from asthma patients compared to control individuals. Conclusions Unlike existing commercial hIL-33 assays, our hIL-33 bioassays are highly sensitive and specific and can accurately quantify hIL-33 in various human clinical matrices, including those with high levels of hsST2. Our results provide a proof of concept of the utility of these assays in clinical trials targeting the hIL-33/hST2 pathway.

The Study of Serum Asymmetric Dimethylarginine Concentrations in the Different Paraoxonase Phenotypes of Exudative Age-related Macular Degeneration Disease

2020 ◽  
Author(s):  
Amir Ghorbanihaghjo ◽  
Shahin Fanalou ◽  
Navid Farahmandian ◽  
Elham Bahreini
Keyword(s):  
Macular Degeneration ◽  
Asymmetric Dimethylarginine ◽  
Oxidized Ldl ◽  
Age Related Macular Degeneration ◽  
Atherogenic Index ◽  
Assay Method ◽  
Pon1 Activity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Lipid Profile ◽  
Age Related

Background and Aims: Age-related macular degeneration (ARMD) is a degenerative retinal disorder that causes progressive loss of central vision in older adults. The study aimed to determine the effect of asymmetric dimethylarginine (ADMA) as oxidizing metabolite and paraoxonase (PON1) activity within its phenotypes as an antioxidant agent in the development of such multifactorial disease. Materials and methods: Forty-five exudative ARMD (E-ARMD) patients and 45 healthy controls were enrolled for this case-control study. Serum PON1 activity was measured using paraoxon and phenylacetate as substrates. PON1 phenotype was determined using the double-substrate method. The ADMA and oxidized LDL (OX-LDL) levels were determined by enzyme-linked immunosorbent assay method. Blood lipid profile was measured, and nontraditional lipid indexes were calculated. Results: Three phenotypes were determined for PON1 among the participants in the study, including AA, AB, and BB phenotypes with low, moderate, and high activity, respectively. AA phenotype was more frequent among E-ARMD, while AB and BB phenotypes were more common among healthy subjects. The mean ADMA and OX-LDL levels were significantly higher in the patients comparing to the controls (p=0.02 and p=0.01, respectively). No significant differences were found in ADMA and OX-LDL levels between phenotypes in each group and also among similar phenotypes. LDL, cholesterol, and even all comprehensive lipid indexes except (atherogenic index of plasma) were higher in E-ARMD patients compared with the healthy group. Conclusions: It was concluded that high-risk individuals could be identified by evaluating the blood factors involved in oxidative stress, and antioxidant therapies may reduce the incidence and progression of the disease.

scholarly journals Circulating salusin-beta levels in the patients with age-related macular degeneration

2021 ◽  
Vol 5 (1) ◽  
pp. 001-004
Author(s):  
Turgut Burak ◽  
Mercan Kadir ◽  
Demir Nesrin ◽  
Ilhan Nevin ◽  
Çatak Onur
Keyword(s):  
Macular Degeneration ◽  
Study Groups ◽  
Age Related Macular Degeneration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Age Related ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
And Gender ◽  
Group 1

Purpose: To evaluate the levels of salusin-beta (β-SAL) in the serum in patients with age-related macular degeneration (ARMD). Methods: Our study was designed as a controlled comparative clinical study. The β-SAL levels in serums of age and sex-matched 20 healthy volunteers as controls (Group 1), 20 patients with dry-age related macular degeneration (d-ARMD) (Group 2) and 20 patients with wet-age related macular degeneration (w-ARMD) (Group 3) were measured with the enzyme-linked immunosorbent assay (ELISA) method. Results: In our study, it was found that age and gender didn’t show a statistically significant difference among the study groups (p > 0. 05). The mean serum β-SAL levels in Group 1, Group 2 and Group 3 were 1372,17 ± 1126.69 pg/mL; 1423,71 ± 1196.84 pg/mL and 940,57 ± 1092.05 pg/mL, respectively. Although the meanβ-SAL levels in w-ARMD seem numerically lower than both the control and d-ARMD groups, this difference among the study groups was not statistically significant (p > 0.05). Conclusion: Our study suggests that β-SAL levels in the patients with ARMD and healthy controls were not different than each other. Further studies with large numbers may reveal possible relationships between β-SAL and ARMD.

scholarly journals The metabolite receptor SUCNR1 in oxidative stress-induced age-related macular degeneration

2020 ◽  
Author(s):  
Elja M.M. Louer ◽  
Peter M.T. Deen ◽  
Anneke I. den Hollander
Keyword(s):  
Oxidative Stress ◽  
Environmental Factors ◽  
Macular Degeneration ◽  
Genetic Susceptibility ◽  
Age Related Macular Degeneration ◽  
Mouse Retina ◽  
Suitable Model ◽  
Age Related ◽  
Susceptibility Factors ◽  
Significant Difference

AbstractAge-related macular degeneration (AMD) is the leading cause of vision impairment in elderly people. AMD is a multifactorial disease which is characterised by complex interactions between metabolic and environmental factors as well as multiple genetic susceptibility factors. The exact mechanism of the most prominent environmental factors, age and smoking, in combination with genetic susceptibility factors is little studied. Here, we set out to study the influence of age, smoking induced oxidative stress and the role of succinate receptor 1 (SUCNR1) in AMD development in mice.Sucnr1 wild-type (WT), heterozygous (HT) and knock-out (KO) mice were exposed to smoking related oxidative stress by the addition of hydroquinone (HQ), the most abundant oxidant in cigarette smoke, to the drinking water of the mice. Using immunohistochemical staining, accumulation of oxidized LDL (oxLDL) in the mouse retina was assessed at 40 and 48 weeks of age.At 40 weeks of age, a significant increase in oxLDL in the Sucnr1 KO mice treated with HQ was observed when compared to the WT and HT mice treated with HQ (p<0.01). However, at 48 weeks, no significant difference was observed between any of the groups. A second experiment analyzing the mice at 40 weeks of age was unable to confirm the observed results of the first experiment.We identified oxLDL accumulations in Sucnr1 KO retinas exposed to HQ, but were unable to repeat this finding. Therefore, under the present conditions, the Sucnr1 KO mouse model is not a suitable model to study AMD development.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 622
Author(s):  
Iswariyaraja Sridevi Gurubaran ◽  
Hanna Heloterä ◽  
Stephen Marry ◽  
Ali Koskela ◽  
Juha M. T. Hyttinen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Macular Degeneration ◽  
Complement Component ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Complement Factor ◽  
Age Related ◽  
Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

scholarly journals Effect of Ranibizumab Treatment in Cases of Choroidal Neovascular Membranes Secondary to Pathological Myopia versus Age-Related Macular Degeneration

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M S Abdaltawab ◽  
Z F Ismail ◽  
W M A Ebeid ◽  
S M Fawzy
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
P Value ◽  
Newly Diagnosed ◽  
Pathological Myopia ◽  
Age Related ◽  
Significant Difference ◽  
The Mean

Abstract Aim of the Work The aim of this work is to compare the response of treatment with ranibizumab in terms of visual acuity in cases of CNV secondary to pathological myopia versus CNV secondary to age-related macular degeneration. Methods This prospective, comparative study included ten eyes newly diagnosed as having CNV secondary to pathological myopia, and 10 eyes newly diagnosed as having subfoveal active CNV secondary to AMD. All patients had 3 monthly intravitreal Injections of 0.50 mg (in 0.05 ml of solution) ranibizumab with monthly evaluation of best corrected visual acuity (BCVA) by Landolt C chart, and also calculated in Logarithm of Minimum Angle of Resolution (Log MAR). Results pretreatment there was no significant difference between the two groups as the mean VA (Log Mar) was 1.31 ± 0.2 in AMD group and 1.17 ± 0.3 in MCNV group of P value = 0.431 and also post three IVI of ranibizumab showed no significant difference between the two groups as the mean VA (Log Mar) was 1.22 ± 0.2 for AMD and 1.22 ± 0.5 for MCNV of P value = 0.635. Conclusion there was no significant difference in BCVA between AMD and MCNV groups after three intravitreal injections of ranibizumab.

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