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

Author(s):  
Amir Ghorbanihaghjo ◽  
Shahin Fanalou ◽  
Navid Farahmandian ◽  
Elham Bahreini

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.

Author(s):  
Kürşad Ramazan Zor ◽  
İsmail Sarı ◽  
Gamze Yıldırım ◽  
İnayet Güntürk ◽  
Erkut Küçük ◽  
...  

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.  


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Elaine Mai ◽  
Joyce Chan ◽  
Levina Goon ◽  
Braeden K. Ego ◽  
Jack Bevers ◽  
...  

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.


2021 ◽  
Vol 15 (1) ◽  
pp. 187-195
Author(s):  
Tatsuya Mimura ◽  
Hideharu Funatsu ◽  
Hidetaka Noma ◽  
Aki Kondo ◽  
Atsushi Mizota

Purpose: The purpose of this study is to compare the aqueous humor level of Silent Information Regulator T1 (SIRT1) between patients with Age-related Macular Degeneration (AMD) and cataract patients. Materials and Methods: Aqueous humor level of SIRT1 was measured by enzyme-linked immunosorbent assay in 13 patients with wet-type AMD (n=13, AMD group) and 13 patients with cataracts (cataract group). In addition, the thickness of each retinal layer was determined by optical coherence tomography. Results: The aqueous humor level of SIRT1 was significantly lower in the AMD group than in the cataract group (p=0.007). In the AMD group, the SIRT1 level was positively correlated with the thickness of the retinal ganglion cell layer (r=0.31) and the inner nuclear layer (r=0.76). Conclusion: The aqueous level of SIRT1 decreased as the ganglion cell layer and inner nuclear layer became thinner, suggesting that reduction of SIRT1 activity might be involved in the pathogenesis of this disease.


2021 ◽  
Vol 18 ◽  
Author(s):  
Priya Battu ◽  
Kaushal Sharma ◽  
Manjari Rain ◽  
Ramandeep Singh ◽  
Akshay Anand

Background: Many factors including genetic and environmental are responsible for the incidence of age-related macular degeneration (AMD). However, its pathogenesis has not been clearly elucidated yet. Objective: This study aimed to estimate the Age-Related Maculopathy Susceptibility 2 (ARMS2), Collagen type VIII Alpha 1 chain (COL8A1), Rad 51 paralog(RAD51B), and Vascular Endothelial Growth Factor (VEGF) protein levels in serum of AMD and control participants and to further investigate their correlation to understand AMD pathogenesis. Methods: For this cross-sectional study, 31 healthy control and 57 AMD patients were recruited from Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A blood sample was taken and serum was isolated from it. ELISA(enzyme-linked immunosorbent assay)was used for the estimation of proteins in the serum of patients. Results: ARMS2 and COL8A1 levels were significantly elevated in the AMD group than in the control group. The highest levels of ARMS2, COL8A1, and VEGF proteins were recorded for the wet AMD sub-group. The study results endorsed significant positive correlation between these following molecules; ARMS2 and COL8A1 (r=0.933, p<0.0001), ARMS2 and RAD51B (r=0.704, p<0.0001), ARMS2 and VEGF (r=0.925, p<0.0001), COL8A1 and RAD51B (r=0.736, p<0.0001), COL8A1 and VEGF (r=0.879, p<0.0001),and RAD51B and VEGF (r=0.691, p<0.0001). Conclusion: The ARMS2 and COL8A1 levels were significantly higher and RAD51B was significantly lower in the AMD group than controls. Also, a significant statistical correlation was detected between these molecules, indicating that their interaction may be involved in the pathogenesis of AMD.


2010 ◽  
Vol 11 (2) ◽  
pp. 49 ◽  
Author(s):  
A. Ghorbanihaghjo ◽  
A. Javadzadeh ◽  
E. Bahreini ◽  
N. Rashtchizadeh ◽  
S. Alizadeh

2015 ◽  
Vol 3 (4) ◽  
pp. 236-243
Author(s):  
Alireza Javadzadeh ◽  
Amir Ghorbanihaghjo ◽  
Sima Mansouri ◽  
Nadereh Rashtchizadeh

2020 ◽  
Author(s):  
Esra Vural ◽  
Leyla Hazar ◽  
Cigdem Karakukçu ◽  
M. Erkam Arslan ◽  
M. Raşit Sirem ◽  
...  

Purpose: To investigate the value of serum apelin-13 levels in age-related macular degeneration patients. Methods: Patients with dry-type AMD, treatment-naive neovascular-type AMD and the healthy control group were included in this study. Patients diagnoses were confirmed with detailed fundus examination, optical cohorence tomography and fundus flourescein angiography findings. Central foveal thickness and subfoveal choroidal thickness were evaluated. Both serum apelin-13 and vascular endothelial growth factor (VEGF) levels were measured by competitive-enzyme-linked immunosorbent assay (ELISA) principle. Results: A total of 84 patients, including 24 patients in the dry-type AMD group (group 1), 27 patients in the neovascular-type AMD (group 2) group and 33 in the control group (group 3) were included in the study. Mean BCVA were 76±4,5, 48,4±16,3, 83,4±3,09 ETDRS letters in groups 1, 2 and 3, respectively. Values of serum VEGF were 44.11±26.14 pg/mL, 56.53±53.77 pg/mL and 61.47±41.62 pg/mL in groups 1, 2 and 3, respectively (p=0.553, p=0.286, p=0.896, respectively). Values of serum apelin-13 were 586.47±167.56 pg/mL, 622.18±324.52 pg/mL, 379. 31±171.96 pg/mL in groups 1, 2 and 3, respectively (p=0.847, p=0.04, p≤0.001, respectively). There was a negative correlation between the value of serum apelin and visual acuity and choroid thickness. Conclusion: Serum apelin-13 were higher in both dry-type AMD patients and neovascular AMD patients compared to the control group. Further studies are needed.


Author(s):  
Turgut Burak ◽  
Mercan Kadir ◽  
Demir Nesrin ◽  
Ilhan Nevin ◽  
Çatak Onur

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Lu Cheng ◽  
Chong Chen ◽  
Wenke Guo ◽  
Kun Liu ◽  
Qianqian Zhao ◽  
...  

Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness, and choroidal neovascularization (CNV) in AMD can lead to serious visual impairment. Gene expression profiling of human ocular tissues have a great potential to reveal the pathophysiology of AMD. This study aimed to identify novel molecular biomarkers and gene expression signatures of AMD.Methods: We analyzed transcriptome profiles in retinal-choroid tissues derived from donor patients with AMD in comparison with those from healthy controls using a publicly available dataset (GSE29801). We focused on the EFEMP1 gene, which was found to be differentially upregulated in AMD, especially in wet AMD eyes. Serological validation analysis was carried out to verify the expression of EFEMP1 in 39 wet AMD patients and 39 age- and gender-matched cataract controls, using an enzyme-linked immunosorbent assay (ELISA). We then investigated the role of EFEMP1 in angiogenesis through in vitro experiments involving EFEMP1 overexpression (OE) and knockdown in human umbilical vein endothelial cells (HUVECs).Results: An increase in EFEMP1 expression was observed in the retinal-choroid tissues of eyes with AMD, which was more significant in wet AMD than in dry AMD. In addition, there was a significant increase in serum fibulin-3 (EFEMP1 encoded protein) concentration in patients with wet AMD compared with that in the controls. Tube formation and proliferation of EFEMP1-OE HUVECs increased significantly, whereas those of EFEMP1 knockdown HUVECs decreased significantly compared with those of the control. Additional extracellular fibulin-3 treatments did not increase tube formation and proliferation of wildtype and EFEMP1 knockdown HUVECs, indicating that the proangiogenic properties of EFEMP1 are of cell origin. We also found that vascular endothelial growth factor expression in HUVECs was upregulated by EFEMP1 overexpression and downregulated by EFEMP1 knockdown.Conclusion: Our findings demonstrate EFEMP1 as a novel biomarker for CNV in AMD, providing a new target for the development of wet AMD-directed pharmaceuticals and diagnostics.


2001 ◽  
Vol 58 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ursula Körner-Stiefbold

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.


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