scholarly journals Pathological Mineralization: The Potential of Mineralomics

Materials ◽  
2019 ◽  
Vol 12 (19) ◽  
pp. 3126 ◽  
Author(s):  
Elena Tsolaki ◽  
Sergio Bertazzo
Keyword(s):  
Materials Science ◽  
Age Related Macular Degeneration ◽  
Science Methods ◽  
Characterization Methods ◽  
Age Related ◽  
New Information ◽  
Wide Range ◽  
Mineralization Processes ◽  
Soft Tissue Diseases ◽  
Prevention Methods

Pathological mineralization has been reported countless times in the literature and is a well-known phenomenon in the medical field for its connections to a wide range of diseases, including cancer, cardiovascular, and neurodegenerative diseases. The minerals involved in calcification, however, have not been directly studied as extensively as the organic components of each of the pathologies. These have been studied in isolation and, for most of them, physicochemical properties are hitherto not fully known. In a parallel development, materials science methods such as electron microscopy, spectroscopy, thermal analysis, and others have been used in biology mainly for the study of hard tissues and biomaterials and have only recently been incorporated in the study of other biological systems. This review connects a range of soft tissue diseases, including breast cancer, age-related macular degeneration, aortic valve stenosis, kidney stone diseases, and Fahr’s syndrome, all of which have been associated with mineralization processes. Furthermore, it describes how physicochemical material characterization methods have been used to provide new information on such pathologies. Here, we focus on diseases that are associated with calcium-composed minerals to discuss how understanding the properties of these minerals can provide new insights on their origins, considering that different conditions and biological features are required for each type of mineral to be formed. We show that mineralomics, or the study of the properties and roles of minerals, can provide information which will help to improve prevention methods against pathological mineral build-up, which in the cases of most of the diseases mentioned in this review, will ultimately lead to new prevention or treatment methods for the diseases. Importantly, this review aims to highlight that chemical composition alone cannot fully support conclusions drawn on the nature of these minerals.

scholarly journals Clinical Perspectives and Trends: Microperimetry as a trial endpoint in retinal disease

2021 ◽  
Author(s):  
Yesa Yang ◽  
Hannah Dunbar
Keyword(s):  
Clinical Trial ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Age Related ◽  
Wide Range ◽  
Trial Endpoints ◽  
Visual Acuity Loss ◽  
Psychophysical Test ◽  
Trial Endpoint

Endpoint development trials are underway across the spectrum of retinal disease. New validated endpoints are urgently required for the assessment of emerging gene therapies and in preparation for the arrival of novel therapeutics targeting early stages of common sight-threatening conditions such as age-related macular degeneration. Visual function measures are likely to be key candidates in this search. Over the last two decades, microperimetry has been used extensively to characterize functional vision in a wide range of retinal conditions, detecting subtle defects in retinal sensitivity that precede visual acuity loss and tracking disease progression over relatively short periods. Given these appealing features, microperimetry has already been adopted as an endpoint in interventional studies, including multicenter trials, on a modest scale. A review of its use to date shows a concurrent lack of consensus in test strategy and a wealth of innovative disease and treatment-specific metrics which may show promise as clinical trial endpoints. There are practical issues to consider, but these have not held back its popularity and it remains a widely used psychophysical test in research. Endpoint development trials will undoubtedly be key in understanding the validity of microperimetry as a clinical trial endpoint, but existing signs are promising.

scholarly journals Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

2014 ◽  
Vol 58 (6) ◽  
pp. 3029-3034 ◽  
Author(s):  
Minh Lam ◽  
Matthew L. Dimaano ◽  
Patricia Oyetakin-White ◽  
Mauricio A. Retuerto ◽  
Jyotsna Chandra ◽  
...  
Keyword(s):  
Liver Toxicity ◽  
Trichophyton Rubrum ◽  
Therapeutic Option ◽  
Age Related Macular Degeneration ◽  
Noninvasive Treatment ◽  
Content Type ◽  
Age Related ◽  
Wide Range ◽  
Silicon Phthalocyanine

ABSTRACTTrichophyton rubrumis the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including age-related macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDTin vitrousing the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2(CH2)3N(CH3)2)(OH)] inT. rubrum. Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 μM Pc 4 followed by 670 to 675 nm light at 2.0 J/cm2reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis.

scholarly journals Herbal Treatments for Age-Related Macular Degeneration: A Literature Review

2020 ◽  
pp. 01-13
Keyword(s):  
Risk Factors ◽  
Medicinal Plants ◽  
Literature Review ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Carnosic Acid ◽  
Retinal Diseases ◽  
Lycium Barbarum ◽  
Age Related ◽  
Wide Range

Background and aim: Age-related macular degeneration (AMD) is one of the major causes of blindness and it has risk factors such as obesity, hypertension, smoking, or genetic characteristics. There is no certain cure for AMD till now, so it is very important to design new therapeutic agents or strategies for treatment of AMD. This literature review assessed the effects of different plants or herbal extracts on the retinal diseases such as AMD either for treatment or prevention of disease. Materials and methods: Fifteen studies were included in this literature review and assessed possible herbal treatments or preventions of AMD or its related diseases and risk factors. Results: From a wide range of medicinal plants, Artemisia annua contained artemisinin, Lycium barbarum, Fructus barbarum rich in carotenoids like zeaxanthin, Scutellaria baicalensis contained wogonin, saffron, rosemary contained carnosic acid, and Melissa officinalis are of the most important and beneficial medicinal plants that can be used for production and design of new drugs and therapeutics for AMD. They act via different mechanisms such as anti-oxidation, anti-VEGF, or anti-inflammatory actions. There are several other important herbal effective compounds for AMD, such as fisetin and luteolin that are polyphenols. Also, there are other herbal compounds such as HESA-A, Traditional Chinese Medicine (TCM), Guibi-tang (GBT), Samul-tang (SMT), and Sipjeondaebo-tang (SDT) that are contained in several different beneficial medicinal plants and their extracts for AMD. Conclusion: There is a need for more investigations on these medicinal plants and their benefits on AMD, but they can be beneficial in lowering the risk of AMD or several other retinal diseases and prevention of them. For each mechanism included in AMD pathogenesis, one or more medicinal plant is introduced in this review.

Opportunities and Challenges in Translational Research: The Development of Photodynamic Therapy and Anti-Vascular Endothelial Growth Factor Drugs

2021 ◽  
Vol 49 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Christina Kaiser Marko ◽  
Joan W. Miller
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Photodynamic Therapy ◽  
Growth Factor ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Vascular Endothelial ◽  
Pharmacological Treatments ◽  
Age Related ◽  
Wide Range ◽  
Endothelial Growth Factor

AbstractThe development of photodynamic therapy and anti-vascular endothelial growth factor agents have revolutionized the treatment of retinal diseases, transforming the retina subspecialty by ushering in an age of pharmacological treatments for a wide range of diseases, including age-related macular degeneration (AMD).

Progress of autophagy in the pathogenesis of dry age-related macular degeneration

2021 ◽  
Vol 2 (4) ◽  
pp. 233-236
Author(s):  
Wen Gao ◽  
Keyword(s):  
Macular Degeneration ◽  
Signaling Pathway ◽  
Age Related Macular Degeneration ◽  
Research Progress ◽  
Related Factor ◽  
Age Related ◽  
Nrf2 Signaling Pathway ◽  
Wide Range ◽  
Mutual Regulation ◽  
New Perspective

Age-related macular degeneration (AMD) is a major clinical blind-inducing eye disease, and its pathogenesis is closely related to the autophagy of RPE cells and the signaling pathway of nuclear factor erythroid-2 related factor 2 (Nrf2). Autophagy is one of the common and important physiological phenomena in human body, which is of vital significance for maintaining the stability and metabolism of cells. Nrf2 is a key transcription factor regulating cells to fight against foreign bodies and oxidative damage, and Nrf2 signaling pathway plays a wide range of cell protective functions in anti-tumor, anti-stress and other aspects. With the development of research, it is found that there are extensive interaction mechanisms between autophagy and Nrf2 signaling pathway. Inhibition of autophagy leads to accumulation of p62, which activates the Nrf2 signaling pathway by binding with Keap1 (kelch-like ech-associated protein1). At the same time, studies have also found that reactive oxygen species (ROS) and other factors also participate in the mutual regulation between autophagy and Nrf2.This paper will review the recent research progress on the interaction between Nrf2 signaling pathway and autophagy in the development of AMD. Hope to provide a new perspective for the treatment of AMD.

scholarly journals Frequent hypomorphic alleles account for a significant fraction of ABCA4 disease and distinguish it from age-related macular degeneration

2017 ◽  
Vol 54 (6) ◽  
pp. 404-412 ◽  
Author(s):  
Jana Zernant ◽  
Winston Lee ◽  
Frederick T Collison ◽  
Gerald A Fishman ◽  
Yuri V Sergeev ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Late Onset ◽  
Direct Sequencing ◽  
Age Related Macular Degeneration ◽  
Imaging Data ◽  
Reading Frame ◽  
Complex Disorders ◽  
Age Related ◽  
Wide Range ◽  
Biallelic Mutations

BackgroundVariation in theABCA4gene is causal for, or associated with, a wide range of phenotypes from early onset Mendelian retinal dystrophies to late-onset complex disorders such as age-related macular degeneration (AMD). Despite substantial progress in determining the causal genetic variation, even complete sequencing of the entire open reading frame and splice sites ofABCA4identifies biallelic mutations in only 60%–70% of cases; 20%–25% remain with one mutation and no mutations are found in 10%–15% of cases with clinically confirmed ABCA4 disease. This study was designed to identify missing causal variants specifically in monoallelic cases of ABCA4 disease.MethodsDirect sequencing and analysis were performed in a large familial ABCA4 disease cohort of predominately European descent (n=643). Patient phenotypes were assessed from clinical and retinal imaging data.ResultsWe determined that a hypomorphicABCA4variant c.5603A>T (p.Asn1868Ile), previously considered benign due to high minor allele frequency (MAF) (~7%) in the general population, accounts for 10% of the disease, >50% of the missing causal alleles in monoallelic cases, ~80% of late-onset cases and distinguishes ABCA4 disease from AMD. It results in a distinct clinical phenotype characterised by late-onset of symptoms (4th decade) and foveal sparing (85%). Intragenic modifying effects involving this variant and another, c.2588G>C (p.Gly863Ala) allele, were also identified.ConclusionsThese findings substantiate the causality of frequent missense variants and their phenotypic outcomes as a significant contribution to ABCA4 disease, particularly the late-onset phenotype, and its clinical variation. They also suggest a significant revision of diagnostic screening and assessment ofABCA4variation in aetiology of retinal diseases.

scholarly journals Synthesis and Biomedical Potential of Azapeptide Modulators of the Cluster of Differentiation 36 Receptor (CD36)

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 241 ◽  
Author(s):  
Caroline Proulx ◽  
Jinqiang Zhang ◽  
David Sabatino ◽  
Sylvain Chemtob ◽  
Huy Ong ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Phagocyte ◽  
Age Related Macular Degeneration ◽  
Murine Models ◽  
Toll Like Receptor ◽  
Age Related ◽  
Wide Range ◽  
Toll Like Receptor 2 ◽  
Cluster Of Differentiation ◽  
Biomedical Potential

The innovative development of azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) has produced selective modulators of the cluster of differentiation 36 receptor (CD36). The azapeptide CD36 modulators curb macrophage-driven inflammation and mitigate atherosclerotic and angiogenic pathology. In macrophages activated with Toll-like receptor-2 heterodimer agonist, they reduced nitric oxide production and proinflammatory cytokine release. In a mouse choroidal explant microvascular sprouting model, they inhibited neovascularization. In murine models of cardiovascular injury, CD36-selective azapeptide modulators exhibited cardioprotective and anti-atherosclerotic effects. In subretinal inflammation models, they altered activated mononuclear phagocyte metabolism and decreased immune responses to alleviate subsequent inflammation-dependent neuronal injury associated with retinitis pigmentosa, diabetic retinopathy and age-related macular degeneration. The translation of GHRP-6 to potent and selective linear and cyclic azapeptide modulators of CD36 is outlined in this review which highlights the relevance of turn geometry for activity and the biomedical potential of prototypes for the beneficial treatment of a wide range of cardiovascular, metabolic and immunological disorders.

scholarly journals Multilabel multiclass classification of OCT images augmented with age, gender and visual acuity data

2018 ◽  
Author(s):  
Parmita Mehta ◽  
Aaron Lee ◽  
Cecilia Lee ◽  
Magdalena Balazinska ◽  
Ariel Rokem
Keyword(s):  
Neural Network ◽  
Visual Acuity ◽  
Macular Degeneration ◽  
Transfer Learning ◽  
Age Related Macular Degeneration ◽  
Multilabel Classification ◽  
Age Related ◽  
Wide Range ◽  
Retinal Pathologies

AbstractOptical Coherence Tomography (OCT) imaging of the retina is in widespread clinical use to diagnose a wide range of retinal pathologies and several previous studies have used deep learning to create systems that can accurately classify retinal OCT as indicative of one of these pathologies. However, patients often exhibit multiple pathologies concurrently. Here, we designed a novel neural network algorithm that performs multiclass and multilabel classification of retinal images from OCT images in four common retinal pathologies: epiretinal membrane, diabetic macular edema, dry age-related macular degeneration and neovascular age-related macular degeneration. Furthermore, clinicians often also use additional information about the patient for diagnosis. Second contribution of this study is improvement of multiclass, multilabel classification augmented with information about the patient: age, visual acuity and gender. We compared two training strategies: a network pre-trained with ImageNet was used for transfer learning, or the network was trained from randomly initialized weights. Transfer learning does not perform better in this case, because many of the low-level filters are tuned to colors, and the OCT images are monochromatic. Finally, we provide a transparent and interpretable diagnosis by highlighting the regions recognized by the neural network.

scholarly journals Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF

2021 ◽  
Vol 22 (21) ◽  
pp. 11317
Author(s):  
Abdullah Al-Ani ◽  
Derek Toms ◽  
Saud Sunba ◽  
Kayla Giles ◽  
Yacine Touahri ◽  
...  
Keyword(s):  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Critical Role ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Wide Range ◽  
And Function

The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal delivery of RPE cells is considered a promising avenue for treatment, and encouraging results from animal trials have supported recent progression into the clinic. However, the limited survival and engraftment of transplanted RPE cells delivered as a suspension continues to be a major challenge. While RPE delivery as epithelial sheets exhibits improved outcomes, this comes at the price of increased complexity at both the production and transplant stages. In order to combine the benefits of both approaches, we have developed size-controlled, scaffold-free RPE microtissues (RPE-µTs) that are suitable for scalable production and delivery via injection. RPE-µTs retain key RPE molecular markers, and interestingly, in comparison to conventional monolayer cultures, they show significant increases in the transcription and secretion of pigment-epithelium-derived factor (PEDF), which is a key trophic factor known to enhance the survival and function of photoreceptors. Furthermore, these microtissues readily spread in vitro on a substrate analogous to Bruch’s membrane, suggesting that RPE-µTs may collapse into a sheet upon transplantation. We anticipate that this approach may provide an alternative cell delivery system to improve the survival and integration of RPE transplants, while also retaining the benefits of low complexity in production and delivery.

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