scholarly journals The Long Pentraxin PTX3 as a New Biomarker and Pharmacological Target in Age-Related Macular Degeneration and Diabetic Retinopathy

2022 ◽  
Vol 12 ◽  
Author(s):  
Matteo Stravalaci ◽  
Mariantonia Ferrara ◽  
Varun Pathak ◽  
Francesca Davi ◽  
Barbara Bottazzi ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Degeneration ◽  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Major Complication ◽  
Age Related Macular Degeneration ◽  
Inflammatory Conditions ◽  
Age Related ◽  
Pharmacological Target ◽  
Underlying Mechanisms

Age related macular degeneration (AMD) and diabetic retinopathy (DR) are multifactorial, neurodegenerative and inflammatory diseases of the eye primarily involving cellular and molecular components of the outer and inner blood-retina barriers (BRB), respectively. Largely contributed by genetic factors, particularly polymorphisms in complement genes, AMD is a paradigm of retinal immune dysregulation. DR, a major complication of diabetes mellitus, typically presents with increased vascular permeability and occlusion of the retinal vasculature that leads, in the proliferative form of the disease, to neovascularization, a pathogenic trait shared with advanced AMD. In spite of distinct etiology and clinical manifestations, both pathologies share common drivers, such as chronic inflammation, either of immune (in AMD) or metabolic (in DR) origin, which initiates and propagates degeneration of the neural retina, yet the underlying mechanisms are still unclear. As a soluble pattern recognition molecule with complement regulatory functions and a marker of vascular damage, long pentraxin 3 (PTX3) is emerging as a novel player in ocular homeostasis and a potential pharmacological target in neurodegenerative disorders of the retina. Physiologically present in the human eye and induced in inflammatory conditions, this protein is strategically positioned at the BRB interface, where it acts as a “molecular trap” for complement, and modulates inflammation both in homeostatic and pathological conditions. Here, we discuss current viewpoints on PTX3 and retinal diseases, with a focus on AMD and DR, the roles therein proposed for this pentraxin, and their implications for the development of new therapeutic strategies.

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 Bone Morphogenetic Proteins and Diabetic Retinopathy

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 593
Author(s):  
Khaled Elmasry ◽  
Samar Habib ◽  
Mohamed Moustafa ◽  
Mohamed Al-Shabrawey
Keyword(s):  
Diabetic Retinopathy ◽  
Bone Morphogenetic Proteins ◽  
Potential Role ◽  
Microvascular Dysfunction ◽  
Cardiovascular Complications ◽  
Bmp Signaling ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Inflammation ◽  
Underlying Mechanisms

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others’ studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

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 prevalence of undiagnosed age-related sight threatening diseases in self-proclaimed healthy individuals

2019 ◽  
Author(s):  
Sophie Lemmens ◽  
João Barbosa Breda ◽  
Karel Van Keer ◽  
Tine Jacobs ◽  
Ruben Van Landeghem ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Degeneration ◽  
Significant Proportion ◽  
Clinical Findings ◽  
Age Related Macular Degeneration ◽  
Ophthalmological Examination ◽  
Healthy Elderly ◽  
Age Related ◽  
Medical Questionnaire

Abstract Background Age-related conditions such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DRP) and cataract have become the major cause of visual impairment and blindness in high-income countries and carry a major socio-economic burden. The aim of the current study is to investigate the prevalence of age-related eye diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy and cataract in a cohort of self-proclaimed healthy elderly, and thus get a rough estimation of the prevalence of undiagnosed age-related eye conditions in the Belgian population.Methods Individuals aged 55 and older without ophthalmological complaints were asked to fill in a general medical questionnaire and underwent an ophthalmological examination, which included a biomicroscopic examination, intraocular pressure measurement, axial length measurement, and acquisition of fundus pictures and Optical Coherence Tomography scans. Information regarding follow-up was collected in the subset of participants who received the advice of referral to an ophthalmologist or the advice to have more frequent follow-up visits, based on the ophthalmological changes detected in their evaluation.Results The cohort included 102 people and comprised 46% men (median age 70 years, range 57-85 years). Referral for additional examinations based on clinical findings, was made in 26 participants (25%). The advice to have more regular follow-up ophthalmologist visits was given to nine additional participants (9%). No significant correlations between baseline characteristics, including eye care consumption, and the need for referral could be identified. Follow-up information was available for 25 out of 26 referred volunteers (96%). Out of these, four (16%) underwent a therapeutical intervention based on study referral, up until 18 months after study participation. All four interventions took place in the age group 65 - 74 years.Conclusions This study shows that even in an elderly population with self-proclaimed healthy eyes and good general health, a significant proportion of subjects showed ocular findings that need regular follow up and/or intervention. Moreover, the frequency of prior ophthalmological examinations does not seem to be relevant to this proportion, meaning that everyone above 55 years old needs a routine ophthalmological evaluation.

scholarly journals Improving Efficiency in Separating Blood Vessels from Retinal Images with Deep Learning Techniques

2019 ◽  
Vol 8 (2S11) ◽  
pp. 3637-3640
Keyword(s):  
Diabetic Retinopathy ◽  
Deep Learning ◽  
Macular Degeneration ◽  
Blood Vessels ◽  
Age Related Macular Degeneration ◽  
Retinal Images ◽  
Retinal Vessels ◽  
Age Related ◽  
Learning Techniques ◽  
Retinal Pathologies

Retinal vessels ID means to isolate the distinctive retinal configuration issues, either wide or restricted from fundus picture foundation, for example, optic circle, macula, and unusual sores. Retinal vessels recognizable proof investigations are drawing in increasingly more consideration today because of pivotal data contained in structure which is helpful for the identification and analysis of an assortment of retinal pathologies included yet not restricted to: Diabetic Retinopathy (DR), glaucoma, hypertension, and Age-related Macular Degeneration (AMD). With the advancement of right around two decades, the inventive methodologies applying PC supported systems for portioning retinal vessels winding up increasingly significant and coming nearer. Various kinds of retinal vessels segmentation strategies discussed by using Deep Learning methods. At that point, the pre-processing activities and the best in class strategies for retinal vessels distinguishing proof are presented.

scholarly journals Epigenetic modifications in hyperhomocysteinemia: potential role in diabetic retinopathy and age-related macular degeneration

Oncotarget ◽  
2018 ◽  
Vol 9 (16) ◽  
pp. 12562-12590 ◽  
Author(s):  
Khaled Elmasry ◽  
Riyaz Mohamed ◽  
Isha Sharma ◽  
Nehal M. Elsherbiny ◽  
Yutao Liu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Degeneration ◽  
Potential Role ◽  
Epigenetic Modifications ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Combined automated screening for age-related macular degeneration and diabetic retinopathy in primary care settings

2021 ◽  
Vol 6 ◽  
pp. 12-12
Author(s):  
Alauddin Bhuiyan ◽  
Arun Govindaiah ◽  
Sharmina Alauddin ◽  
Oscar Otero-Marquez ◽  
R. Theodore Smith
Keyword(s):  
Primary Care ◽  
Diabetic Retinopathy ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Primary Care Settings ◽  
Age Related ◽  
Automated Screening
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