scholarly journals Cellular Consequences of Coenzyme Q10 Deficiency in Neurodegeneration of the Retina and Brain

2020 ◽  
Vol 21 (23) ◽  
pp. 9299
Author(s):  
Haider Manzar ◽  
Dalia Abdulhussein ◽  
Timothy E. Yap ◽  
M. Francesca Cordeiro
Keyword(s):  
Coenzyme Q10 ◽  
Cellular Level ◽  
Vital Role ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Inner Mitochondrial Membrane ◽  
Waste Products ◽  
Age Related ◽  
Coq10 Deficiency ◽  
The Central Nervous System

Coenzyme Q10 (CoQ10) is a ubiquitous cofactor in the body, operating in the inner mitochondrial membrane, where it plays a vital role in the generation of adenosine triphosphate (ATP) through the electron transport chain (ETC). In addition to this, CoQ10 serves as an antioxidant, protecting the cell from oxidative stress by reactive oxygen species (ROS) as well as maintaining a proton (H+) gradient across lysosome membranes to facilitate the breakdown of cellular waste products. Through the process of ageing, the body becomes deficient in CoQ10, resulting in several systemic manifestations. On a cellular level, one of the consequences of CoQ10 deficiency is apoptosis, which can be visualised in tissues of the central nervous system (CNS). Diseases affecting the retina and brain such as age-related macular degeneration (AMD), glaucoma, Alzheimer’s disease (AD) and Parkinson’s disease (PD) have shown defects in cellular biochemical reactions attributed to reduced levels of CoQ10. Through further research into the pathogenesis of such conditions, the effects of CoQ10 deficiency can be counteracted through supplementation, early detection and intervention.

scholarly journals Age-Related, Sport-Specific Adaptions of the Shoulder Girdle in Elite Adolescent Tennis Players

2014 ◽  
Vol 49 (5) ◽  
pp. 647-653 ◽  
Author(s):  
Ann M. Cools ◽  
Tanneke Palmans ◽  
Fredrik R. Johansson
Keyword(s):  
Muscle Strength ◽  
Shoulder Girdle ◽  
Vital Role ◽  
The Body ◽  
Injury Incidence ◽  
Shoulder Injury ◽  
Serratus Anterior ◽  
Cross Sectional ◽  
Tennis Players ◽  
Age Related

Context Tennis requires repetitive overhead movements that can lead to upper extremity injury. The scapula and the shoulder play a vital role in injury-free playing. Scapular dysfunction and glenohumeral changes in strength and range of motion (ROM) have been associated with shoulder injury in the overhead athlete. Objective To compare scapular position and strength and shoulder ROM and strength between Swedish elite tennis players of 3 age categories (<14, 14–16, and >16 years). Design Cross-sectional study. Setting Tennis training sports facilities. Patients or Other Participants Fifty-nine adolescent Swedish elite tennis players (ages 10–20 years) selected based on their national ranking. Main Outcome Measure(s) We used a clinical screening protocol with a digital inclinometer and a handheld dynamometer to measure scapular upward rotation at several angles of arm elevation, isometric scapular muscle strength, glenohumeral ROM, and isometric rotator cuff strength. Results Players older than 16 years showed less scapular upward rotation on the dominant side at 90° and 180° (P < .05). Although all absolute scapular muscle strength values increased with age, there was no change in the body-weight–normalized strength of the middle (P = .9) and lower (P = .81) trapezius or serratus anterior (P = .17). Glenohumeral internal-rotation ROM and total ROM tended to decrease, but this finding was not statistically significant (P = .052 and P = .06, respectively). Whereas normalized internal-rotator strength increased from 14 to 16 years to older than 16 years (P = .009), normalized external-rotator and supraspinatus strength remained unchanged. Conclusions Age-related changes in shoulder and scapular strength and ROM were apparent in elite adolescent tennis players. Future authors should examine the association of these adaptations with performance data and injury incidence.

scholarly journals Potential Treatment of Retinal Diseases with Iron Chelators

2018 ◽  
Vol 11 (4) ◽  
pp. 112 ◽  
Author(s):  
Wanting Shu ◽  
Joshua Dunaief
Keyword(s):  
Retinal Degeneration ◽  
Therapeutic Potential ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Hereditary Diseases ◽  
Iron Chelators ◽  
Excess Iron ◽  
Age Related

Iron is essential for life, while excess iron can be toxic. Iron generates hydroxyl radical, which is the most reactive free radical, causing oxidative stress. Since iron is absorbed through the diet but not excreted from the body, it accumulates with age in tissues, including the retina, consequently leading to age-related toxicity. This accumulation is further promoted by inflammation. Hereditary diseases such as aceruloplasminemia, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, and posterior column ataxia with retinitis pigmentosa involve retinal degeneration associated with iron dysregulation. In addition to hereditary causes, dietary or parenteral iron supplementation has been recently reported to elevate iron levels in the retinal pigment epithelium (RPE) and promote retinal degeneration. Ocular siderosis from intraocular foreign bodies or subretinal hemorrhage can also lead to retinopathy. Evidence from mice and humans suggests that iron toxicity may contribute to age-related macular degeneration pathogenesis. Iron chelators can protect photoreceptors and RPE in various mouse models. The therapeutic potential for iron chelators is under investigation.

scholarly journals Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress

2021 ◽  
Vol 14 (8) ◽  
pp. 1260-1273
Author(s):  
Zi-Yan Cai ◽  
◽  
Ke Liu ◽  
Xuan-Chu Duan ◽  
◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vision Loss ◽  
Eye Diseases ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Classical Pathway ◽  
Age Related ◽  
Important Relationship

Age-related eye diseases, including cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are the leading causes of vision loss in the world. Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye. The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body. This pathway is also active in the development of age-related eye diseases. A variety of drugs have been shown to treat age-related eye diseases through the Keap1-Nrf2-ARE (Kelch-like ECH-Associating protein 1- nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway. This review describes the role of oxidative stress in the development of age-related eye diseases, the function and regulation of the Keap1-Nrf2-ARE pathway, and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.

scholarly journals Neuroprotective Potential of Ginkgo biloba in Retinal Diseases

Planta Medica ◽  
2019 ◽  
Vol 85 (17) ◽  
pp. 1292-1303 ◽  
Author(s):  
Isabel Martínez-Solís ◽  
Nuria Acero ◽  
Francisco Bosch-Morell ◽  
Encarna Castillo ◽  
María Eugenia González-Rosende ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ginkgo Biloba ◽  
Redox Homeostasis ◽  
Antioxidant Properties ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Age Related ◽  
The Central Nervous System ◽  
Degenerative Processes

AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.

Bruch’s membrane pathology: A mechanistic perspective

2020 ◽  
Vol 30 (6) ◽  
pp. 1195-1206 ◽  
Author(s):  
Aishwarya Murali ◽  
Subramanian Krishnakumar ◽  
Anuradha Subramanian ◽  
Sowmya Parameswaran
Keyword(s):  
Extracellular Matrix ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Vital Role ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Age Related

Bruch’s membrane, an extracellular matrix located between the retinal pigment epithelium and the choroid, plays a vital role as structural and functional support to the retinal pigment epithelium. Dysfunction of Bruch’s membrane in both age-related macular degeneration and other ocular diseases is caused mostly by extracellular matrix degeneration, deposit formation, and angiogenesis. Although these factors are dealt in greater detail with respect to the cells that are degenerated such as the retinal pigment epithelium and the endothelial cells, the pathology involving the Bruch’s membrane is often underrated. Since in most of the macular degenerations early degenerative changes are also observed in the Bruch’s membrane, addressing only the cellular component without the underlying membrane will not yield an ideal clinical benefit. This review aims to discuss the factors and the mechanisms affecting the integrity of the Bruch’s membrane, which would aid in developing an effective therapy for these pathologies.

scholarly journals Ophthalmology: ozone therapy applied to dystrophic maculopathy

Ozone Therapy ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Giorgio Grechi
Keyword(s):  
The Body ◽  
Age Related Macular Degeneration ◽  
Antioxidant Systems ◽  
Macular Area ◽  
Ozone Therapy ◽  
Rods And Cones ◽  
Age Related ◽  
Small Structure ◽  
Colloid Cysts ◽  
The Brain

The macula, which is the noblest part of the retina, is a very small structure, containing the photoreceptors (rods and cones) responsible for visual acuity. Over the years, observations have confirmed that alterations that modify the optimal state of the eye also give rise to similar diseases in the brain: ischemias, structural circulatory alterations and neurodegeneration. As the body ages, oxidative alterations take place and they change the antioxidant systems that serves as a neurological and ocular defence. In industrialised nations, age-related macular degeneration is the leading cause of blindness in patients over 55 years of age. Initially, this creates drusen (or colloid cysts) in the macular area.

scholarly journals Oxidative stress alters transcript localization of disease-causing genes in the retinal pigment epithelium

2021 ◽  
Author(s):  
Tadeusz J Kaczynski ◽  
Elizabeth D Au ◽  
Michael H Farkas
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Nuclear Retention ◽  
Age Related

Nuclear retention is a mechanism whereby RNA transcripts are held in the nucleus to maintain a proper nuclear-to-cytoplasmic balance or as a stockpile for use in responding to stimuli. Many mechanisms are employed to determine whether transcripts are retained or exported to the cytoplasm, though the extent to which tissue- or cell-type, stressors, or disease pathogenesis affect this process remains unclear. As the most biochemically active tissue in the body, the retina must mitigate endogenous and exogenous stressors to maintain cell health and tissue function. Oxidative stress, believed to contribute to the pathogenesis, or progression, of age-related macular degeneration (AMD) and inherited retinal dystrophies (IRDs), is produced both internally from biochemical processes, as well as externally from environmental insult. To evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), we performed poly-A RNA sequencing on nuclear and cytoplasmic fractions from induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide, as well as untreated controls. Under normal conditions, the number of mRNA transcripts retained in the nucleus exceeded that found in studies of other tissues. Further, the nuclear-to-cytoplasmic ratio of transcripts is altered following oxidative stress, as is the retention of genes associated with AMD, IRDs, and those important for RPE physiology. These results provide a retention catalog of all expressed mRNA in iPSC-RPE under normal conditions and after exposure to hydrogen peroxide, offering insight into one of the potential roles oxidative stress plays in the progression of visual disorders.

scholarly journals Brain lymphatic drainage system – visualization opportunities and current state of the art

2020 ◽  
Vol 9 (3) ◽  
pp. 81-89
Author(s):  
G. S. Yankova ◽  
O. B. Bogomyakova
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Surveillance ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Lymphatic Drainage ◽  
Waste Products ◽  
Glymphatic System ◽  
Age Related ◽  
The Central Nervous System ◽  
The Brain

The lymphatic drainage system of the brain is assumed to consist of the lymphatic system and a network of meningeal lymphatic vessels. This system supports brain homeostasis, participates in immune surveillance and presents a new therapeutic target in the treatment of neurological disorders.The article analyzes and systematizes data on the brain lymphatic drainage system. The key components of this system are considered: recently described meningeal lymphatic vessels and their relationship with the glymphatic system, which provides perfusion of the central nervous system with cerebrospinal and interstitial fluids. The lymphatic drainage system helps to maintain water and ion balances of the interstitial fluid and to remove metabolic waste products, assists in reabsorption of macromolecules. Disorders in its work play a crucial role in age-related changes in the brain, the pathogenesis of neurovascular and neurodegenerative diseases, as well as injuries and brain tumors. The review also presents the results of human studies concerning the presence, anatomy and structure of meningeal lymphatic vessels and the glymphatic system. The discovery of the brain lymphatic drainage system has not only changed our understanding of cerebrospinal fluid circulation, but also contributed to understanding the pathology and mechanisms of neurodegenerative diseases.

RADIATION-PROTECTIVE AGENT AND ANTI-AGING AGENTS: RANDOM AND PREDICTABLE MATCHES

2020 ◽  
pp. 646-656
Author(s):  
В. Н. Быков ◽  
А. Н. Гребенюк ◽  
И. Б. Ушаков
Keyword(s):  
Cell Cycle ◽  
Ionizing Radiation ◽  
Antioxidant Activities ◽  
Early Stage ◽  
Cellular Level ◽  
The Body ◽  
Protective Agent ◽  
Age Related ◽  
Short Term Exposure ◽  
Time Required

Радиопротекторные и геропротекторные свойства соединений нередко сочетаются, что может быть обусловлено общими механизмами действия: антиоксидантной активностью, повышением устойчивости к клеточному стрессу, ускорением репарации ДНК, предотвращением хронических воспалительных заболеваний и канцерогенеза. В данной работе приведен детальный анализ молекулярнобиологических механизмов действия препаратов, обладающих радиопротекторными и/или геропротекторными свойствами. Описаны общие звенья развития старения и патогенеза заболеваний, связанных с облучением, включающие активацию свободнорадикальных реакций, нарушение регуляции репарации ДНК, клеточного цикла и апоптоза. С одной стороны, на фоне остановки клеточного цикла и блокады апоптоза увеличивается время для репарации ДНК. С другой стороны, активация апоптоза измененных клеток рассматривается как один из механизмов замедления процессов старения и предотвращения отдаленных эффектов воздействия ионизирующих излучений. Выделено две основных группы радиозащитных препаратов: 1) обладающие антиапоптозным свойством и способствующие повышению выживаемости в ранние сроки после после облучения в высокой дозе; 2) способствующие элиминированию поврежденных клеток (сенолитики) и наиболее эффективные при длительном низкодозовом воздействии радиации или фракционированном облучении. Геропротекторная активность описана для препаратов второй группы, к которым относятся мелатонин, метформин, рапамицин и природные полифенольные соединения. Radiation-protective and anti-aging properties are often combined. Combination of this properties is linked to the common mechanisms of action such as direct and indirect antioxidant activities, inhibition of free radicals formation, increase resistance to stress impacts at the cellular level, acceleration of DNA reparation, prevention of chronic diseases linked to abnormalities in regeneration processes, activation of immune inflammatory processes and carcinogenesis. Regulation of cell cycle and apoptosis can often be considered as an implementing driver of radiation-protective and anti-aging activities. On the one hand, against the background of stopping the cell cycle and blockade of apoptosis increases the time required to repair the defects of a DNA. Antiapoptotic effects enhances survival chances at the early stage after irradiation in a particular range of doses. On the other hand, activation of apoptosis of altered cells can be seen as one of the mechanisms to delay aging processes and prevention of isolated effects of exposure to ionizing radiation. Formation of radiation-induced and age-related alterations are characterized by multiple factors and a variety of manifestations. Nevertheless, similarity of individual links of the pathogenesis of disease related to radiation exposure and aging of the body is striking. It could be stated that radiation-protective property defines an increase in life expectancy by short-term exposure in sub-lethal and lethal doses. However anti-aging activities prevent the development of remote effects of ionizing radiation by prolonged low doses or fractionated exposure to radiation.

scholarly journals The Aging Stress Response and Its Implication for AMD Pathogenesis

2020 ◽  
Vol 21 (22) ◽  
pp. 8840
Author(s):  
Janusz Blasiak ◽  
Elzbieta Pawlowska ◽  
Anna Sobczuk ◽  
Joanna Szczepanska ◽  
Kai Kaarniranta
Keyword(s):  
Stress Response ◽  
Vision Loss ◽  
The Elderly ◽  
Cellular Level ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Nutrient Signaling ◽  
Amp Activated Protein Kinase

Aging induces several stress response pathways to counterbalance detrimental changes associated with this process. These pathways include nutrient signaling, proteostasis, mitochondrial quality control and DNA damage response. At the cellular level, these pathways are controlled by evolutionarily conserved signaling molecules, such as 5’AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), insulin/insulin-like growth factor 1 (IGF-1) and sirtuins, including SIRT1. Peroxisome proliferation-activated receptor coactivator 1 alpha (PGC-1α), encoded by the PPARGC1A gene, playing an important role in antioxidant defense and mitochondrial biogenesis, may interact with these molecules influencing lifespan and general fitness. Perturbation in the aging stress response may lead to aging-related disorders, including age-related macular degeneration (AMD), the main reason for vision loss in the elderly. This is supported by studies showing an important role of disturbances in mitochondrial metabolism, DDR and autophagy in AMD pathogenesis. In addition, disturbed expression of PGC-1α was shown to associate with AMD. Therefore, the aging stress response may be critical for AMD pathogenesis, and further studies are needed to precisely determine mechanisms underlying its role in AMD. These studies can include research on retinal cells produced from pluripotent stem cells obtained from AMD donors with the mutations, either native or engineered, in the critical genes for the aging stress response, including AMPK, IGF1, MTOR, SIRT1 and PPARGC1A.

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