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.

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 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 Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1455
Author(s):  
Emilio Iturriaga-Goyon ◽  
Beatriz Buentello-Volante ◽  
Fátima Sofía Magaña-Guerrero ◽  
Yonathan Garfias
Keyword(s):  
Clinical Trials ◽  
Macular Degeneration ◽  
Small Molecules ◽  
Inflammatory Diseases ◽  
Age Related Macular Degeneration ◽  
Future Perspectives ◽  
Whole Cells ◽  
Pathological Angiogenesis ◽  
Age Related ◽  
Viral Particles

Aptamers are single-stranded DNA or RNA oligonucleotides that are currently used in clinical trials due to their selectivity and specificity to bind small molecules such as proteins, peptides, viral particles, vitamins, metal ions and even whole cells. Aptamers are highly specific to their targets, they are smaller than antibodies and fragment antibodies, they can be easily conjugated to multiple surfaces and ions and controllable post-production modifications can be performed. Aptamers have been therapeutically used for age-related macular degeneration, cancer, thrombosis and inflammatory diseases. The aim of this review is to highlight the therapeutic, diagnostic and prognostic possibilities associated with aptamers, focusing on eye pathological angiogenesis.

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.

scholarly journals Efficacy Comparison of Intravitreal Anti-VEGF Therapy for Three Subtypes of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jianqing Li ◽  
Jiayi Xu ◽  
Yiyi Chen ◽  
Jiaju Zhang ◽  
Yihong Cao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Macular Degeneration ◽  
Meta Analysis ◽  
Age Related Macular Degeneration ◽  
Cochrane Library ◽  
Anti Vegf ◽  
Age Related ◽  
Significant Difference ◽  
The Mean

Purpose. Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy has been widely used for the treatment of neovascularization (NV) secondary to age-related macular degeneration (AMD). This study aimed to compare the efficacy among different subtypes of neovascular age-related macular degeneration (nAMD). Methods. PubMed, Embase, and the Cochrane Library were searched for eligible studies. We performed meta-analysis using Review Manager 5.3 and Stata/SE 12.0. Results. A total of 24 studies met our inclusion criteria and were included in the systematic review. At 3 months, the mean logarithm of the minimum angle of resolution (logMAR) improvements were −0.09, −0.18, and −0.23 for type 1, 2, and 3, respectively, while the mean macular thickness (MT) changes were −104.83, −130.76, and −196.29 μm. At 12 months, the mean changes in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters were 6.38, 8.12, and 9.37, while the MT decrease was 126.51, 126.52, and 139.85 μm, respectively. However, statistically significant difference was only found between type 1 and 3 in vision improvement, both in the short term (p=0.0002) and long term (p=0.01). Conclusions. The reactivity to VEGF inhibitors varied among different subtypes of nAMD. The efficacy of intravitreal anti-VEGF therapy in type 3 nAMD was statistically better than type 1 when considering vision improvement at 3 and 12 months. Thus, the lesion subtype is a predictor for the treatment outcome which can help guide prognosis.

Intravitreal bevacizumab treatment for neovascular age-related macular degeneration and thromboembolic events

2019 ◽  
Vol 30 (1) ◽  
pp. 66-71
Author(s):  
Orly Weinstein ◽  
Muhammad Abu Tailakh ◽  
Tova Lifshitz ◽  
Victor Novack ◽  
Jaime Levy
Keyword(s):  
Acute Coronary Syndrome ◽  
Macular Degeneration ◽  
Intravitreal Bevacizumab ◽  
Age Related Macular Degeneration ◽  
Thromboembolic Events ◽  
Coronary Syndrome ◽  
Intravitreal Bevacizumab Injection ◽  
Age Related ◽  
Significant Difference ◽  
Bevacizumab Injection

Background: Systemic complications of intravitreal anti-vascular endothelial growth factor agents are relatively uncommon but highly significant. Objectives: Primary objective: To assess the risk for thromboembolic events following intravitreal bevacizumab injection in neovascular age-related macular degeneration patients by a large population-based study. Secondary objective: To analyze the association between injection frequency and the risk for thromboembolic events, the time interval between the injection and the thromboembolic events, and the influence of chronic diseases on complications rate. Design: A retrospective cohort study. Methods: Consecutive neovascular age-related macular degeneration patients receiving intravitreal bevacizumab at Soroka University Medical Center from December 2005 to December 2013 were included. Thromboembolic events analyzed included acute coronary syndrome, acute myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism. The thromboembolic event rate was compared 2 years prior and 2 years after the initial intravitreal bevacizumab injection. Results: A total of 2102 patients were included. Acute coronary syndrome and stroke rate were higher 2 years after intravitreal bevacizumab (p = 0.03 and p = 0.01, respectively). No statistical significant difference was found for the rest of thromboembolic events. Patients older than 80 years and patients receiving less than six intravitreal bevacizumab injections were more likely to experience stroke. Patients with known cardiovascular risk factors before starting injections did not develop significant more thromboembolic events. Conclusion: In our study population, patients treated with intravitreal bevacizumab were significantly more likely to experience stroke during 2 years after first injection.

scholarly journals Investigation of the Trend of Selecting Anti-Vascular Endothelial Growth Factor Agents for the Initial Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

2021 ◽  
Vol 10 (16) ◽  
pp. 3580
Author(s):  
Jae-Hui Kim ◽  
Jong-Woo Kim ◽  
Chul-Gu Kim
Keyword(s):  
Macular Degeneration ◽  
Initial Treatment ◽  
Polypoidal Choroidal Vasculopathy ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Significant Difference ◽  
Treatment Naïve ◽  
Treatment Agent ◽  
Type 3 ◽  
Choroidal Vasculopathy

BACKGROUND: This study aimed to investigate the trend of selecting ranibizumab and aflibercept for the initial treatment of neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This was a retrospective study that included 460 patients who were diagnosed with treatment-naïve neovascular AMD and PCV and were initially treated with either ranibizumab or aflibercept. The patients were divided into two groups: the ranibizumab group (n = 96) and the aflibercept group (n = 324). The patients’ characteristics and the proportion of the subtypes of macular neovascularization (MNV) were compared between the two groups. RESULTS: Patients in the ranibizumab group were significantly older (mean 74.3 ± 8.4 years) than those in the aflibercept group (mean 70.4 ± 8.8 years; p < 0.001). In the ranibizumab group, the proportions of type 1 or 2 MNV, type 3 MNV, and PCV were 50.0%, 27.1%, and 22.9%, respectively. In the aflibercept group, the proportions were 35.2%, 6.8%, and 58.0%, respectively. There was a significant difference in the proportion of MNV subtypes between the ranibizumab and aflibercept groups (p < 0.001). Ranibizumab was used in 54.2% of patients with type 3 MNVs. However, in patients with PCV, aflibercept was used in 89.5% of patients. CONCLUSIONS: Ranibizumab was preferred as an initial treatment agent in older patients and those with type 3 MNV, whereas aflibercept was highly preferred in patients with PCV. The different characteristics and efficacy of the two agents may have partially contributed to this trend.

scholarly journals Silent Information Regulator T1 in Aqueous Humor of Patients with Age-Related Macular Degeneration

2021 ◽  
Vol 15 (1) ◽  
pp. 187-195
Author(s):  
Tatsuya Mimura ◽  
Hideharu Funatsu ◽  
Hidetaka Noma ◽  
Aki Kondo ◽  
Atsushi Mizota
Keyword(s):  
Ganglion Cell ◽  
Macular Degeneration ◽  
Aqueous Humor ◽  
Ganglion Cell Layer ◽  
Cell Layer ◽  
Inner Nuclear Layer ◽  
Age Related Macular Degeneration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Retinal Layer ◽  
Age Related

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.

scholarly journals Switching from Intravitreal Ranibizumab to Bevacizumab for Age-Related Macular Degeneration

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Kisaburo Yamada ◽  
Kenichi Kimoto ◽  
Hirofumi Kono ◽  
Toshiaki Kubota
Keyword(s):  
Macular Degeneration ◽  
Intravitreal Bevacizumab ◽  
Age Related Macular Degeneration ◽  
Rank Test ◽  
Intravitreal Ranibizumab ◽  
Age Related ◽  
Signed Rank ◽  
Significant Difference ◽  
Signed Rank Test ◽  
Ranibizumab Treatment

Purpose. To report our experiences in patients with age-related macular degeneration (AMD) treated initially with intravitreal ranibizumab and then switched to bevacizumab. Methods. We retrospectively reviewed the records of 7 patients (7 eyes) who were treated with monthly injections of intravitreal ranibizumab and then switched to injections of bevacizumab (every 6 weeks) for six months. The best-corrected visual acuity measurements (BCVA) and optical coherence tomography (OCT) were performed at the baseline examination and then at each visit. The Wilcoxon signed-rank test was used for the statistical analysis. Results. Following three monthly ranibizumab treatments, there was no significant difference in the BCVA, while the foveal retinal thickness (FRT) significantly decreased (). Switching from ranibizumab to bevacizumab resulted in maintenance (57.2%) of the BCVA and a further decrease in the FRT () after 6 months. Conclusions. Switching to intravitreal bevacizumab may be effective in patients who wish to discontinue intravitreal ranibizumab treatment due to the high cost.

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