scholarly journals The leukotriene receptors as therapeutic targets of inflammatory diseases

2019 ◽  
Vol 31 (9) ◽  
pp. 607-615 ◽  
Author(s):  
Fumiyuki Sasaki ◽  
Takehiko Yokomizo
Keyword(s):  
Inflammatory Diseases ◽  
Gene Knockout ◽  
Age Related Macular Degeneration ◽  
Bronchial Smooth Muscle ◽  
Age Related ◽  
Pharmacological Studies ◽  
Gene Knockout Mice ◽  
Leukotriene Receptors ◽  
Acute And Chronic Inflammation ◽  
Ltb4 Receptor

Abstract Leukotrienes (LTs) are inflammatory mediators derived from arachidonic acid. LTs include the di-hydroxy acid LT (LTB4) and the cysteinyl LTs (CysLTs; LTC4, LTD4 and LTE4), all of which are involved in both acute and chronic inflammation. We and other groups identified a high-affinity LTB4 receptor, BLT1; the LTC4 and LTD4 receptors, CysLT1 and CysLT2; and the LTE4 receptor, GPR99. Pharmacological studies have shown that BLT1 signaling stimulates degranulation, chemotaxis and phagocytosis of neutrophils, whereas CysLT1 and CysLT2 signaling induces airway inflammation by increasing vascular permeability and the contraction of bronchial smooth muscle. Recently, we and other groups suggested that the LTB4–BLT1 axis and the cysteinyl LTs–CysLT1/2 axis are involved in chronic inflammatory diseases including asthma, atopic dermatitis, psoriasis, atherosclerosis, arthritis, obesity, cancer and age-related macular degeneration using animal models for disease and gene knockout mice. This review describes the classical and novel functions of LTs and their receptors in several inflammatory diseases and discusses the potential clinical applications of antagonists for LT receptors and inhibitors of LT biosynthesis.

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 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 The Contribution of Fluoride to the Pathogenesis of Eye Diseases: Molecular Mechanisms and Implications for Public Health

2019 ◽  
Vol 16 (5) ◽  
pp. 856 ◽  
Author(s):  
Declan Waugh
Keyword(s):  
Risk Factors ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Hsp70 Expression ◽  
Modifiable Risk Factors ◽  
Factors Associated ◽  
Age Related ◽  
Lines Of Evidence

This study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect by inhibiting enolase, τ-crystallin, Hsp40, Na+, K+-ATPase, Nrf2, γ -GCS, HO-1 Bcl-2, FoxO1, SOD, PON-1 and glutathione activity, and upregulating NF-κB, IL-6, AGEs, HsP27 and Hsp70 expression. Moreover, F exposure leads to enhanced oxidative stress and impaired antioxidant activity. Based on the evidence presented in this study, it can be concluded that F exposure may be added to the list of identifiable risk factors associated with pathogenesis of degenerative eye diseases. The broader impact of these findings suggests that reducing F intake may lead to an overall reduction in the modifiable risk factors associated with degenerative eye diseases. Further studies are required to examine this association and determine differences in prevalence rates amongst fluoridated and non-fluoridated communities, taking into consideration other dietary sources of F such as tea. Finally, the findings of this study elucidate molecular pathways associated with F exposure that may suggest a possible association between F exposure and other inflammatory diseases. Further studies are also warranted to examine these associations.

scholarly journals Critical evaluation of the off-label indication and of the risks associated to the use of multi-dose vials on the treatment of age-related macular degeneration

2014 ◽  
Vol 50 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Bruna Renata Dutra Barbosa ◽  
Sávio Fujita Barbosa ◽  
Guilherme Diniz Tavares ◽  
Nádia Araci Bou Chacra ◽  
Terezinha de Jesus Andreoli Pinto
Keyword(s):  
Macular Degeneration ◽  
Therapeutic Indication ◽  
Inflammatory Diseases ◽  
Critical Evaluation ◽  
Age Related Macular Degeneration ◽  
Public Consultation ◽  
Off Label ◽  
Age Related ◽  
Ophthalmic Therapy ◽  
Label Indication

Age-related macular degeneration (AMD) is an ocular inflammatory diseases treated mainly by means of a bevacizumab (Avastin®) or ranibizumab (Lucentis®) intravitreal injection. Among these drugs, only ranibizumab has a specific therapeutic indication for AMD. Considering that, the off-label use on ophthalmic therapy seems to become a rule when it should be an exception. Furthermore, bevacizumab presentation consists of multi-dose vials although it does not contain preservatives in its formula. The current literature review aimed at assessing the risks for the patient related to the use of off-label indication and multi-dose vials on AMD treatment. Considering this, the proposal related to the Brazilian Public Consultation no.10, dated September 12, 2012, which proposes the Clinical Protocol and Therapeutic Guidelines for AMD treatment, was evaluated. This systematic review allowed to conclude that the bevacizumab off-label indication results in increased risks for the patient when compared to the product with specific therapeutic indication for AMD treatment (ranibizumab), especially referring to the significant raise in the adverse events. The risks for the patient related to the multi-dose vial use, referring to the microbiological stability and dose precision, were also made clear.

Modern Imaging Techniques for Visualising Choroidal Morphology and Function

2021 ◽  
Vol 238 (09) ◽  
pp. 951-961
Author(s):  
Marion Munk ◽  
Chantal Dysli
Keyword(s):  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Diagnostic Techniques ◽  
Age Related Macular Degeneration ◽  
Basic Knowledge ◽  
Pathologic Myopia ◽  
Age Related ◽  
And Function

AbstractThe choroid is directly adjacent to the retina and consists of a dense vascular network that supplies the outer retina. Pathologies in the choroid can lead to changes in the retinal pigment epithelium (RPE) and photoreceptors. Thus, the choroid plays a crucial role in the development of retinal diseases such as age-related macular degeneration (AMD), central serous chorioretinopathy (CSCR), pathologic myopia, and inflammatory diseases such as Vogt-Koyanagi-Harada syndrome (VKH). Basic knowledge of the structure and physiology of the choroid, as well as diagnostic options for visualizing choroidal changes, provides a better understanding of the physiology and pathology of choroidal processes. This review provides an overview of the anatomy and function of the choroid, and describes the diagnostic techniques currently available to characterize and visualize the choroid. It also includes an overview of various retinal conditions, which are associated with choroidal changes.

scholarly journals PEDF expression affects the oxidative and inflammatory state of choroidal endothelial cells

2018 ◽  
Vol 314 (4) ◽  
pp. C456-C472 ◽  
Author(s):  
Mitra Farnoodian ◽  
Christine M. Sorenson ◽  
Nader Sheibani
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Inflammatory Diseases ◽  
Expression Profiles ◽  
Pigment Epithelium ◽  
Age Related Macular Degeneration ◽  
Primary Role ◽  
Age Related ◽  
Inflammatory State ◽  
The Impact

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly population, and is associated with severe macular degeneration and choroidal neovascularization (CNV). Although the pathogenesis of AMD is associated with choroidal dysfunction and CNV, the detailed underlying mechanisms remain unresolved. Altered production of pigment epithelium-derived factor (PEDF), a neuroprotective and antiangiogenic factor, contributes to CNV. Furthermore, exogenous PEDF mitigates angiogenesis in preclinical CNV models. How PEDF expression affects choroidal endothelial cell (ChEC) function is unknown. Here we isolated ChECs from PEDF+/+ and PEDF-deficient (PEDF−/−) mice and determined the impact of PEDF expression on the proangiogenic and pro-inflammatory properties of ChECs. We showed that PEDF expression significantly affects the proliferation, migration, adhesion, and oxidative and inflammatory state of ChECs. The PEDF−/− ChECs were, however, more sensitive to H2O2 challenge and exhibited increased rate of apoptosis and oxidative stress. We also observed a significant increase in production of cytokines with a primary role in inflammation and angiogenesis including vascular endothelial growth factor (VEGF) and osteopontin, and a reprograming of chemokines and cytokines expression profiles in PEDF−/− ChECs. Collectively, our results indicate that PEDF expression has a significant impact on oxidative and inflammatory properties of ChECs, whose alteration could contribute to pathogenesis of chronic inflammatory diseases including exudative AMD.

scholarly journals Role of intestinal microbiome in the pathogenesis of age-related macular degeneration

2020 ◽  
Vol 1 (1) ◽  
pp. 29-36
Author(s):  
Dimitrios Kalogeropoulos ◽  
Konstantinos Katsikatsos ◽  
Konstantinos Dallas ◽  
Soon Wai Ch’ng ◽  
Ioannis Asproudis ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Intestinal Microbiota ◽  
English Language ◽  
Inflammatory Diseases ◽  
Active Role ◽  
Age Related Macular Degeneration ◽  
Intestinal Microbiome ◽  
Therapeutic Modalities ◽  
Age Related

Background: The microbiome is strongly linked to many extra-intestinal disorders. Gut commensal microbiota, in particular, plays an active role in human immune and intestinal homeostasis. Complex interactions of the microbiota with host genetics and other underlying factors lead to intestinal dysbiosis, which is thought to be linked to ocular inflammatory diseases. Thus, the aim of this review is to analyze the role of intestinal microbiome in age-related macular degeneration (AMD). Methods: A thorough literature search was performed using PubMed/MEDLINE, limited to English language publications, from January 2004 to March 2020. An additional search was made employing Google Scholar to complete the collected data as per the above-mentioned time-line and language limitations. The main keywords used included age-related macular degeneration, microbiome, dysbiosis, autoimmunity, gut microbiota, epigenetics, immune-mediated inflammatory diseases, and gut-retina axis. Results: Recent studies have proposed the role of intestinal microbiota in the pathogenesis of AMD. Changes in the microbiome have been shown to trigger several ocular inflammatory processes. There is increasing evidence demonstrating that intestinal microbial imbalance may play an important role in the pathogenesis of AMD. Conclusions: This review summarizes how alterations in the intestinal microbiota can be associated with the pathogenesis of AMD and how new therapeutic modalities can be designed to target this microbiome to limit the severe nature of this disease. Future advances in microbiome research may unveil a new era in understanding and managing AMD.

scholarly journals ALGORITHM OF DIAGNOSTICS AND TREATMENT OF AN AGE-RELATED MACULAR DEGENERATION AT PATIENTS WITH CHRONIC PERIPHERAL UVEITIS

2014 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Yu. I. Khoroshikh ◽  
O. I. Krivosheina ◽  
Ye. V. Melekhin
Keyword(s):  
Macular Degeneration ◽  
Inflammatory Process ◽  
Inflammatory Diseases ◽  
Age Related Macular Degeneration ◽  
Screening Methods ◽  
Age Related ◽  
Different Types ◽  
Exudative Macular Degeneration ◽  
Peripheral Areas ◽  
Practical Recommendations

The results of clinical trial of various approaches in treatment the exudative forms of macular degenerations, including age-related, against chronic slow intensity inflammatory process on the extreme retinal periphery of an eye are described in represented material. There were 91 patients (105 eyes) in the research with different types of an exudative macular degeneration. The general criteria of inclusion were: age of 18–80 years old, complaints to discomfort in eyes, a spot before an eye, distortions and decrease in the central sight, ophthalmoscopic symptoms of hypostasis in the central and peripheral areas of a retina. It is analyzed the general criteria of diagnostics and treatment of the disease in the article. Considering defeat of the chorioretinal structures located near the ora serrata at persons of young and advanced age. Practical recommendations to a choice of methods of diagnostics and treatment of various clinical and morphological forms of the disease are made. Screening methods of identification of patients with the peripheral uveitis are offered. The scheme of risk calculation of development the macular pathology at persons with changes on the extreme periphery of a retina, that can be used as a method of prevention of development predictively adverse of “wet" forms of an age-related macular degeneration, by means of timely sparing treatment at patients with chronic inflammatory diseases of eyes is given.

scholarly journals Indocyanine Green Angiography

2017 ◽  
pp. 28-31
Keyword(s):  
Indocyanine Green ◽  
Central Serous Chorioretinopathy ◽  
Indocyanine Green Angiography ◽  
Imaging Technique ◽  
Inflammatory Diseases ◽  
Age Related Macular Degeneration ◽  
Imaging Findings ◽  
Age Related ◽  
Vascular Structures ◽  
Healthy Eyes

Indocyanine green angiography is an imaging technique used to determine the characteristics of choroidal vascular structures and choroidal pathologies. There are a lot of clinical uses in diseases such as central serous chorioretinopathy, choroidal inflammatory diseases, and choroidal tumors, especially in age-related macular degeneration. In this review, we present the general features and typical imaging findings provided by the Indocyanine green angiography in healthy eyes and the above-mentioned diseases.

scholarly journals Fibromodulin Ablation Exacerbates the Severity of Acute DSS Colitis

2022 ◽  
Author(s):  
Marianna Halasi ◽  
Mor Grinstein ◽  
Avner Adini ◽  
Irit Adini
Keyword(s):  
Clinical Symptoms ◽  
Inflammatory Diseases ◽  
Epidemiological Studies ◽  
Age Related Macular Degeneration ◽  
Type I ◽  
Acute Colitis ◽  
Activated T Cells ◽  
Dss Colitis ◽  
Age Related ◽  
Potential Biomarker

Epidemiological studies have linked pigment production to protection against certain human diseases. In contrast to African Americans, European descendants are more likely to suffer from angiogenesis-dependent diseases, and inflammatory diseases such as wet age-related macular degeneration (ARMD) and ulcerative colitis (UC), respectively. Here, we found that albino mice producing high levels of fibromodulin (FMOD) developed less severe acute colitis than mice lacking FMOD as assessed by the clinical symptoms and the histopathological changes. In a dextran sodium sulfate (DSS)-induced acute colitis mouse model, depletion of FMOD affected the expression and localization of tight junction proteins contributing to destruction of the epithelial barrier. Furthermore, this study demonstrates the development of a stronger inflammatory response after DSS treatment in the absence of FMOD. FMOD depletion led to an increase in activated T cells, plasmacytoid dendritic cells (pDCs), and type I IFN production. These findings strongly suggest that FMOD may serve as a potential biomarker in determining disease severity of UC in the population of light-skinned individuals with European descent.

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