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Lipofuscin

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https://www.readbyqxmd.com/read/29473871/impaired-cargo-clearance-in-the-retinal-pigment-epithelium-rpe-underlies-irreversible-blinding-diseases
#1
REVIEW
Eloise Keeling, Andrew J Lotery, David A Tumbarello, J Arjuna Ratnayaka
Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways lead to the accumulation of lipofuscin and pyridinium bis-retinoid A2E aggregates and chemically modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE...
February 23, 2018: Cells
https://www.readbyqxmd.com/read/29458079/autofluorescence-a-potential-pitfall-in-immunofluorescence-based-inflammation-grading
#2
Jonas Wizenty, Muhammad Imtiaz Ashraf, Nadine Rohwer, Martin Stockmann, Sascha Weiss, Matthias Biebl, Johann Pratschke, Felix Aigner, Tilo Wuensch
Immunofluorescence (IF) staining of paraffin-embedded tissues is a frequently used method to answer research questions or even detect the abundance of a certain protein for diagnostic use. However, the signal originating from specific antibody-staining might be distorted by autofluorescence (AF) of the assessed tissue. Although the AF phenomenon is well known, its presence is often neglected by insufficient staining controls. In this study, we describe the existence of cellular AF in paraffin-embedded healthy and inflamed human and murine colonic tissues and present ways to reduce AF...
February 16, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29444484/application-of-a-new-targeted-low-density-microarray-and-conventional-biomarkers-to-evaluate-the-health-status-of-marine-mussels-a-field-study-in-sardinian-coast-italy
#3
Susanna Sforzini, Caterina Oliveri, Andrea Orrù, Giannina Chessa, Beniamina Pacchioni, Caterina Millino, Awadhesh N Jha, Aldo Viarengo, Mohamed Banni
In the present study, we investigated the health status of marine mussels (Mytilus galloprovincialis) caged and deployed at three different sites on the Sardinian coastline characterized by different levels of contamination: Fornelli (F, the reference site), Cala Real (CR), and Porto Torres (PT). A new low density oligonucleotide microarray was used to investigate global gene expression in the digestive gland of mussels. Target genes were selected to cover most of the biological processes involved in the stress response in bivalve mollusks (e...
February 11, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29439995/primary-photodynamic-therapy-with-verteporfin-for-pigmented-posterior-pole-ct1a-choroidal-melanoma-a-3-year-retrospective-analysis
#4
Ido Didi Fabian, Andrew W Stacey, Lamis Al Harby, Amit K Arora, Mandeep S Sagoo, Victoria M L Cohen
AIMS: To investigate the outcomes of primary photodynamic therapy (PDT) for pigmented posterior pole cT1a choroidal melanoma. METHODS: Retrospective interventional consecutive case series of 26 patients (26 eyes) with pigmented posterior pole cT1a choroidal melanoma, who were treated with 3 sessions of PDT and followed-up thereafter. RESULTS: Included were 11 males and 15 females that presented at a median age of 66 years (mean: 64) with transformed naevi (n=11) or suspicious lesions (n=15) with ≥3 risk factors for growth, with lipofuscin in all...
February 13, 2018: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29415988/photosensitization-of-a2e-triggers-telomere-dysfunction-and-accelerates-retinal-pigment-epithelium-senescence
#5
Jing Wang, Yiji Feng, Peng Han, Fenghua Wang, Xueting Luo, Jian Liang, Xiangjun Sun, Jing Ye, Yiming Lu, Xiaodong Sun
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in elderly people. AMD is classified as early, intermediate, advanced non-neovascular, and advanced neovascular forms depending on the clinical features. However, the exact pathogenesis remains unclear. Retinal pigment epithelium (RPE) cells degeneration is a hallmark of AMD. With aging, lipofuscin accumulates in RPE cells. N-retinylidene-N-retinylethanolamine (named A2E), a well-known fluorophore of lipofuscin, may contribute to RPE cells degeneration...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29414672/recombinant-buckwheat-glutaredoxin-intake-increases-lifespan-and-stress-resistance-via-hsf-1-upregulation-in-caenorhabditis-elegans
#6
Fang Li, Xiaoli Ma, Xiaodong Cui, Jiao Li, Zhuanhua Wang
Glutaredoxin (Grx) is a polypeptide with low molecular weight, which has been extracted from buckwheat and has been suggested to have multiple functions revolving around oxidative stress responses and cell signaling. Here, we report the antioxidant activity of recombinant buckwheat Grx (rbGrx) to reduce aging effects in Caenorhabditis elegans as well as the mechanism involved. Our results showed that rbGrx beneficially affected the health span of C. elegans, including pharyngeal-pumping rate, locomotion, and lipofuscin accumulation...
February 4, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29397579/%C3%AE-motor-neurons-are-spared-from-aging-while-their-synaptic-inputs-degenerate-in-monkeys-and-mice
#7
Nicholas Maxwell, Ryan W Castro, Natalia M Sutherland, Kelli L Vaughan, Mark D Szarowicz, Rafael de Cabo, Julie A Mattison, Gregorio Valdez
Motor function deteriorates with advancing age, increasing the risk of adverse health outcomes. While it is well established that skeletal muscles and neuromuscular junctions (NMJs) degenerate with increasing age, the effect of aging on α-motor neurons and their innervating synaptic inputs remains largely unknown. In this study, we examined the soma of α-motor neurons and innervating synaptic inputs in the spinal cord of aged rhesus monkeys and mice, two species with vastly different lifespans. We found that, in both species, α-motor neurons retain their soma size despite an accumulation of large amounts of cellular waste or lipofuscin...
February 4, 2018: Aging Cell
https://www.readbyqxmd.com/read/29358124/a2e-associated-cell-death-and-inflammation-in-retinal-pigmented-epithelial-cells-from-human-induced-pluripotent-stem-cells
#8
Vipul M Parmar, Tanu Parmar, Eisuke Arai, Lindsay Perusek, Akiko Maeda
Accumulation of lipofuscin in the retinal pigmented epithelium (RPE) is observed in retinal degenerative diseases including Stargardt disease and age-related macular degeneration. Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) is a major component of lipofuscin. A2E has been implicated in RPE atrophy and retinal inflammation; however, mice with A2E accumulation display only a mild retinal phenotype. In the current study, human iPSC-RPE (hiPSC-RPE) cells were generated from healthy individuals to examine effects of A2E in human RPE cells...
January 12, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29327028/transition-metals-and-trace-elements-in-the-retinal-pigment-epithelium-and-choroid-correlative-ultrastructural-and-chemical-analysis-by-analytical-electron-microscopy-and-nano-secondary-ion-mass-spectrometry
#9
Antje Biesemeier, Oliver Eibl, Santhana Eswara, Jean-Nicolas Audinot, Tom Wirtz, Ulrich Schraermeyer
Understanding the localisation and abundance of structural elements, trace elements and especially transition metals like Cu and Zn in ocular tissue sections is important for physiology, and also for the characterisation of diseases related to oxidative stress like age-related macular degeneration. Transition metal abundances were investigated in an aged donor eye by nano-secondary ion mass spectrometry (nano-SIMS) elemental mapping using Cs+ and O- primary ions, respectively, and correlated to their respective mole fractions investigated by analytical electron microscopy (AEM)...
January 12, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29324592/frequent-subclinical-macular-changes-in-combined-braf-mek-inhibition-with-high-dose-hydroxychloroquine-as-treatment-for-advanced-metastatic-braf-mutant-melanoma-preliminary-results-from-a-phase-i-ii-clinical-treatment-trial
#10
Akosua A Nti, Leona W Serrano, Harpal S Sandhu, Katherine E Uyhazi, Ilaina D Edelstein, Elaine J Zhou, Scott Bowman, Delu Song, Tara C Gangadhar, Lynn M Schuchter, Sheryl Mitnick, Alexander Huang, Charles W Nichols, Ravi K Amaravadi, Benjamin J Kim, Tomas S Aleman
PURPOSE: To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. METHODS: Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment...
January 10, 2018: Retina
https://www.readbyqxmd.com/read/29319194/ageing-of-the-carotid-body
#11
Camillo Di Giulio
The ageing process is characterized by a decline in several physiological functions resulting in a reduced capability to maintain homeostasis. The lowered homeostatic capacity seems to involve the carotid body (CB), whose role is to modulate ventilation and tissue oxygen supply. It thus plays a prime role in all ageing processes. Ageing causes marked changes in CB morphology. In older animals, it is enlarged and shows a concomitant decrease in the percentage of chemoreceptor tissue, as well as a proliferation of type II cells...
January 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29317248/cognitive-decline-and-increased-hippocampal-p-tau-expression-in-mice-with-hearing-loss
#12
So Young Park, Min Jung Kim, Hong Lim Kim, Dong Kee Kim, Sang Won Yeo, Shi Nae Park
Hearing and cognition are commonly involved in both normal and pathological aging. Current clinical interest lies in whether peripheral hearing loss promotes cognitive decline. In our previous publication, the authors have shown a causal relationship between hearing and cognitive impairments in C57BL/6 mice. Here we extended the follow-up to 12 months to determine the long-term effects of hearing loss on cognition and to observe hippocampal p-tau and lipofuscin. One month old male mice were randomly allocated into two groups, the control (n = 12) and noise-induced hearing loss (NIHL) (n = 12)...
January 6, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29229934/bis-monoacylglycero-phosphate-lipids-in-the-retinal-pigment-epithelium-implicate-lysosomal-endosomal-dysfunction-in-a-model-of-stargardt-disease-and-human-retinas
#13
David M G Anderson, Zsolt Ablonczy, Yiannis Koutalos, Anne M Hanneken, Jeffrey M Spraggins, M Wade Calcutt, Rosalie K Crouch, Richard M Caprioli, Kevin L Schey
Stargardt disease is a juvenile onset retinal degeneration, associated with elevated levels of lipofuscin and its bis-retinoid components, such as N-retinylidene-N-retinylethanolamine (A2E). However, the pathogenesis of Stargardt is still poorly understood and targeted treatments are not available. Utilizing high spatial and high mass resolution matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS), we determined alterations of lipid profiles specifically localized to the retinal pigment epithelium (RPE) in Abca4 -/- Stargardt model mice compared to their relevant background strain...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222621/lifespan-extension-of-caenorhabditis-elegans-by-butyricicoccus-pullicaecorum-and-megasphaera-elsdenii-with-probiotic-potential
#14
Gayeung Kwon, Jiyun Lee, Jong-Ho Koh, Young-Hee Lim
Butyricicoccus pullicaecorum and Megasphaera elsdenii inhabit the human intestine and have probiotic potential. The aim of this study was to evaluate the effects of B. pullicaecorum and M. elsdenii on the lifespan of Caenorhabditis elegans. They significantly (P < 0.05) extended the lifespan of C. elegans compared with Escherichia coli OP50, a standard food for the worm. Analysis of age-related biomarkers such as lipofuscin, body size, and locomotory activity showed that they retarded aging. They all failed to extend the lifespan of daf-12 or dbl-1 loss-of-function C...
December 8, 2017: Current Microbiology
https://www.readbyqxmd.com/read/29214314/quantitative-fundus-autofluorescence-in-pseudoxanthoma-elasticum
#15
Martin Gliem, Philipp L Müller, Johannes Birtel, Myra B McGuinness, Robert P Finger, Philipp Herrmann, Doris Hendig, Frank G Holz, Peter Charbel Issa
Purpose: To quantify lipofuscin-associated fundus autofluorescence in patients with pseudoxanthoma elasticum (PXE), a model disease for Bruch's membrane pathology. Methods: In this prospective, monocenter, cross-sectional case-control study, 49 patients with PXE (mean age: 46 years, range 18-62) underwent quantitative fundus autofluorescence (qAF) imaging with a modified scanning laser ophthalmoscope containing an internal fluorescent reference for normalization of images...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29210183/young-plasma-reverses-age-dependent-alterations-in-hepatic-function-through-the-restoration-of-autophagy
#16
Anding Liu, Enshuang Guo, Jiankun Yang, Yan Yang, Shenpei Liu, Xiaojing Jiang, Qi Hu, Olaf Dirsch, Uta Dahmen, Cuntai Zhang, David A Gewirtz, Haoshu Fang
Recent studies showing the therapeutic effect of young blood on aging-associated deterioration of organs point to young blood as the solution for clinical problems related to old age. Given that defective autophagy has been implicated in aging and aging-associated organ injuries, this study was designed to determine the effect of young blood on aging-induced alterations in hepatic function and underlying mechanisms, with a focus on autophagy. Aged rats (22 months) were treated with pooled plasma (1 ml, intravenously) collected from young (3 months) or aged rats three times per week for 4 weeks, and 3-methyladenine or wortmannin was used to inhibit young blood-induced autophagy...
December 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/29192807/autophagy-in-advanced-low-and-high-grade-tubular-adenocarcinomas-of-the-stomach-an-ultrastructural-investigation
#17
Rosario Alberto Caruso, Giuseppe Angelico, Eleonora Irato, Rosalba de Sarro, Giovanni Tuccari, Antonio Ieni
Autophagy represents a catabolic process in which cellular protein and organelles are engulfed into autophagosomes, digested in lysosomes and reutilized for the cellular metabolism. In neoplastic conditions, autophagy may act either as a tumour suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumour growth. Although enhanced autophagy has been reported in hypoxic areas of solid tumors, there are only few ultrastructural reports concerning the relationships between autophagy and tumor grade...
December 1, 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29189906/individual-variability-in-the-structural-properties-of-neurons-in-the-human-inferior-olive
#18
Joan S Baizer, Keit Men Wong, Chet C Sherwood, Patrick R Hof, Sandra F Witelson
The inferior olive (IO) is the sole source of the climbing fibers innervating the cerebellar cortex. We have previously shown both individual differences in the size and folding pattern of the principal nucleus (IOpr) in humans as well as in the expression of different proteins in IOpr neurons. This high degree of variability was not present in chimpanzee samples. The neurochemical differences might reflect static differences among individuals, but might also reflect age-related processes resulting in alterations of protein synthesis...
November 30, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29150629/statistically-strong-label-free-quantitative-identification-of-native-fluorophores-in-a-biological-sample
#19
Saabah B Mahbub, Martin Plöschner, Martin E Gosnell, Ayad G Anwer, Ewa M Goldys
Bioimaging using endogenous cell fluorescence, without any external biomarkers makes it possible to explore cells and tissues in their original native state, also in vivo. In order to be informative, this label-free method requires careful multispectral or hyperspectral recording of autofluorescence images followed by unsupervised extraction (unmixing) of biochemical signatures. The unmixing is difficult due to the scarcity of biochemically pure regions in cells and also because autofluorescence is weak compared with signals from labelled cells, typically leading to low signal to noise ratio...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29149899/selective-depletion-of-microglial-progranulin-in-mice-is-not-sufficient-to-cause-neuronal-ceroid-lipofuscinosis-or-neuroinflammation
#20
Terri L Petkau, Natalia Kosior, Kathleen de Asis, Colúm Connolly, Blair R Leavitt
BACKGROUND: Progranulin deficiency due to heterozygous null mutations in the GRN gene are a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations are thought to be a rare cause of neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout (Grn-null) mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. In the brain, progranulin is predominantly expressed in neurons and microglia, and previously, we demonstrated that neuronal-specific depletion of progranulin does not recapitulate the neuropathological phenotype of Grn-null mice...
November 17, 2017: Journal of Neuroinflammation
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