scholarly journals Experimental Models of Glaucoma: A Powerful Translational Tool for the Future Development of New Therapies for Glaucoma in Humans—A Review of the Literature

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 280 ◽  
Author(s):  
Karine Evangelho ◽  
Claudio A. Mastronardi ◽  
Alejandra de-la-Torre
Keyword(s):  
Animal Models ◽  
Clinical Application ◽  
Complex Disease ◽  
Ganglion Cells ◽  
Experimental Period ◽  
The Elderly ◽  
Clinical Results ◽  
Experimental Models ◽  
Common Complex Disease ◽  
Age Related

Glaucoma is a common complex disease that leads to irreversible blindness worldwide. Even though preclinical studies showed that lowering intraocular pressure (IOP) could prevent retinal ganglion cells loss, clinical evidence suggests that lessening IOP does not prevent glaucoma progression in all patients. Glaucoma is also becoming more prevalent in the elderly population, showing that age is a recognized major risk factor. Indeed, recent findings suggest that age-related tissue alterations contribute to the development of glaucoma and have encouraged exploration for new treatment approaches. In this review, we provide information on the most frequently used experimental models of glaucoma and describe their advantages and limitations. Additionally, we describe diverse animal models of glaucoma that can be potentially used in translational medicine and aid an efficient shift to the clinic. Experimental animal models have helped to understand the mechanisms of formation and evacuation of aqueous humor, and the maintenance of homeostasis of intra-ocular pressure. However, the transfer of pre-clinical results obtained from animal studies into clinical trials may be difficult since the type of study does not only depend on the type of therapy to be performed, but also on a series of factors observed both in the experimental period and the period of transfer to clinical application. Conclusions: Knowing the exact characteristics of each glaucoma experimental model could help to diminish inconveniences related to the process of the translation of results into clinical application in humans.

Inherited glaucoma in DBA/2J mice: Pertinent disease features for studying the neurodegeneration

2005 ◽  
Vol 22 (5) ◽  
pp. 637-648 ◽  
Author(s):  
RICHARD T. LIBBY ◽  
MICHAEL G. ANDERSON ◽  
IOK-HOU PANG ◽  
ZACHARY H. ROBINSON ◽  
OLGA V. SAVINOVA ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cells ◽  
The Elderly ◽  
Nerve Degeneration ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Future Studies ◽  
Age Related ◽  
Iop Elevation ◽  
Mechanistic Basis

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8–9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.

scholarly journals Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Samuel Abokyi ◽  
Chi-Ho To ◽  
Tim T. Lam ◽  
Dennis Y. Tse
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Macular Degeneration ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Vascular Endothelial ◽  
Age Related ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly. There are very limited therapeutic options for AMD with the predominant therapies targeting vascular endothelial growth factor (VEGF) in the retina of patients afflicted with wet AMD. Hence, it is important to remind readers, especially those interested in AMD, about current studies that may help to develop novel therapies for other stages of AMD. This study, therefore, provides a comprehensive review of studies on human specimens as well as rodent models of the disease, to identify and analyze the molecular mechanisms behind AMD development and progression. The evaluation of this information highlights the central role that oxidative damage in the retina plays in contributing to major pathways, including inflammation and angiogenesis, found in the AMD phenotype. Following on the debate of oxidative stress as the earliest injury in the AMD pathogenesis, we demonstrated how the targeting of oxidative stress-associated pathways, such as autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, might be the futuristic direction to explore in the search of an effective treatment for AMD, as the dysregulation of these mechanisms is crucial to oxidative injury in the retina. In addition, animal models of AMD have been discussed in great detail, with their strengths and pitfalls included, to assist inform in the selection of suitable models for investigating any of the molecular mechanisms.

scholarly journals Repository of proposed pathways and protein–protein interaction networks in age-related macular degeneration

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Fran M. Pool ◽  
Christina Kiel ◽  
Luis Serrano ◽  
Philip J. Luthert
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Protein Interaction ◽  
Complex Disease ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Age Related

AbstractAge-related macular degeneration (AMD) is one of the commonest causes of sight loss in the elderly population and to date there is no intervention that slows or prevents early AMD disease progressing to blinding neovascularization or geographic atrophy. AMD is a complex disease and factors proposed to contribute to the development and progression of disease include aging, genetics, epigenetics, oxidative stress, pro-inflammatory state, and life-style factors such as smoking, alcohol, and high fat diet. Here, we generate a knowledge repository of pathways and protein–protein interaction (PPI) networks likely to be implicated in AMD pathogenesis, such as complement activation, lipid trafficking and metabolism, vitamin A cycle, oxidative stress, proteostasis, bioenergetics, autophagy/mitophagy, extracellular matrix (ECM) turnover, and choroidal vascular dropout. Two disctinct clusters ermerged from the networks for parainflamation and ECM homeostasis, which may represent two different disease modules underlying AMD pathology. Our analyses also suggest that the disease manifests primarily in RPE/choroid and less in neural retina. The use of standardized syntax when generating maps of these biological processes (SBGN standard) and networks (PSI standard) enables visualization of complex information in graphical programs such as CellDesigner and Cytoscape and enhances reusability and extension of data. The ability to focus onto subnetworks, multiple visualizations and simulation options will enable the AMD research community to computationally model subnetworks or to test experimentally new hypotheses arising from connectivities in the AMD pathway map.

scholarly journals Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 824
Author(s):  
Andrea Capucciati ◽  
Fabio A. Zucca ◽  
Enrico Monzani ◽  
Luigi Zecca ◽  
Luigi Casella ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Brain Aging ◽  
Experimental Models ◽  
Test Tube ◽  
Age Related ◽  
And Function ◽  
Endogenous Metabolites ◽  
High Degree

Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics. However, disturbances of NM synthesis and function could be toxic. Here, we review recent knowledge on NM formation, toxic mechanisms involving NM, go over NM binding substances and suggest experimental models that can help identifying xenobiotic modulators of NM formation or function. Given the high likelihood of a central NM role in age-related human neurodegenerative diseases such as Parkinson’s and Alzheimer’s, resembling such diseases using animal models that do not form NM to a high degree, e.g., mice or rats, may not be optimal. Rather, use of animal models (i.e., sheep and goats) that better resemble human brain aging in terms of NM formation, as well as using human NM forming stem cellbased in vitro (e.g., mid-brain organoids) models can be more suitable. Toxicants could also be identified during chemical synthesis of NM in the test tube.

Aging and cardioprotection

2007 ◽  
Vol 103 (6) ◽  
pp. 2120-2128 ◽  
Author(s):  
Arshad Jahangir ◽  
Sandeep Sagar ◽  
Andre Terzic
Keyword(s):  
Animal Models ◽  
Healthy Aging ◽  
Myocardial Dysfunction ◽  
Experimental Studies ◽  
Structural Heart Disease ◽  
The Elderly ◽  
Therapeutic Interventions ◽  
Limited Information ◽  
Aging Heart ◽  
Age Related

Advanced age is a strong independent predictor for death, disability, and morbidity in patients with structural heart disease. With the projected increase in the elderly population and the prevalence of age-related cardiovascular disabilities worldwide, the need to understand the biology of the aging heart, the mechanisms for age-mediated cardiac vulnerability, and the development of strategies to limit myocardial dysfunction in the elderly have never been more urgent. Experimental evidence in animal models indicate attenuation in cardioprotective pathways with aging, yet limited information is available regarding age-related changes in the human heart. Human cardiac aging generates a complex phenotype, only partially replicated in animal models. Here, we summarize current understanding of the aging heart stemming from clinical and experimental studies, and we highlight targets for protection of the vulnerable senescent myocardium. Further progress mandates assessment of human tissue to dissect specific aging-associated genomic and proteomic dynamics, and their functional consequences leading to increased susceptibility of the heart to injury, a critical step toward designing novel therapeutic interventions to limit age-related myocardial dysfunction and promote healthy aging.

How Can Genetic Advances Impact on Experimental Models of Encapsulating Peritoneal Sclerosis?

2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 16-20 ◽  
Author(s):  
Angela M. Summers ◽  
Catherine M. Hoff ◽  
Nicholas Topley
Keyword(s):  
Animal Models ◽  
Molecular Biology ◽  
Disease Progression ◽  
Interventional Procedures ◽  
Complex Disease ◽  
Experimental Models ◽  
Genetic Technologies

In this review we discuss how animal models have contributed to the understanding of pathological pathways that may be involved in the development of encapsulating peritoneal sclerosis. We review the various interventional procedures that, so far, have ameliorated disease progression in animals. Reviewing advancements in molecular biology and genetic technologies, we discuss how future experimental models may impact our understanding of the pathogenesis and treatment of this rare but complex disease.

scholarly journals Animal models of memory impairment

1997 ◽  
Vol 352 (1362) ◽  
pp. 1711-1717 ◽  
Author(s):  
◽  
Michela Gallagher
Keyword(s):  
Animal Models ◽  
Spatial Memory ◽  
Memory Impairment ◽  
Structural Integrity ◽  
Hippocampal Formation ◽  
Cholinergic Neurons ◽  
The Elderly ◽  
Aged Rats ◽  
Young Rats ◽  
Age Related

Memory impairment in the elderly resembles a mild temporal lobe dysfunction. Alterations in the hippocampal formation are also a probable basis for cognitive deficits in some animal models of ageing. For example, aged rats are impaired in hippocampal-dependent tests of spatial memory. Recent studies have revealed considerable structural integrity in the aged hippocampus, even in aged rats with the most impaired spatial memory. In contrast, atrophy/loss of cholinergic neurons in the basal forebrain and deficiency in cholinergic transduction in hippocampus correlate with the severity of spatial memory impairment in aged rats. This evidence supports the longstanding view that age-related loss of memory has a cholinergic basis. In this context, it is somewhat surprising that the use of a selective cholinergic immunotoxin in young rats to further test this hypothesis has revealed normal spatial memory after removing septo-hippocampal cholinergic neurons. Young rats with immunotoxic lesions, however, have other behavioural impairments in tests of attentional processing. These lines of research have implications for understanding the neurobiological basis of memory deficits in ageing and for selecting an optimal behavioural setting in which to examine therapies aimed at restoring neurobiological function.

The Biological Clock and Sleep in the Elderly

2006 ◽  
Vol 19 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Myriam Juda ◽  
Mirjam Münch ◽  
Anna Wirz-Justice ◽  
Martha Merrow ◽  
Till Roenneberg
Keyword(s):  
Circadian Rhythms ◽  
Biological Clock ◽  
The Elderly ◽  
Early Morning ◽  
Behavioral Changes ◽  
Older Age ◽  
Age Related ◽  
Theoretical Considerations ◽  
Sleep Difficulties ◽  
Circadian Biology

Abstract: Among many other changes, older age is characterized by advanced sleep-wake cycles, changes in the amplitude of various circadian rhythms, as well as reduced entrainment to zeitgebers. These features reveal themselves through early morning awakenings, sleep difficulties at night, and a re-emergence of daytime napping. This review summarizes the observations concerning the biological clock and sleep in the elderly and discusses the documented and theoretical considerations behind these age-related behavioral changes, especially with respect to circadian biology.

What Can We Learn from Sarcopenia with Curarisation in the Context of Cancer Surgery? A Review of the Literature

2019 ◽  
Vol 25 (28) ◽  
pp. 3005-3010
Author(s):  
Georges Samouri ◽  
Alexandre Stouffs ◽  
Lionel V. Essen ◽  
Olivier Simonet ◽  
Marc De Kock ◽  
...  
Keyword(s):  
Frail Elderly ◽  
Muscle Fibers ◽  
Motor Units ◽  
The Elderly ◽  
Hepatic Function ◽  
Volume Of Distribution ◽  
Neuromuscular Blocking ◽  
Cancer Surgery ◽  
Old People ◽  
Age Related

Introduction: The monitoring of the curarisation is a unique opportunity to investigate the function of the neuromuscular junction (NMJ) during cancer surgery, especially in frailty-induced and age-related sarcopenia. Method: We conducted a comprehensive literature review in PubMed, without any limit of time related to frailty, sarcopenia, age and response to neuromuscular blockers in the context of cancer surgery. Results: Several modifications appear with age: changes in cardiac output, a decrease in muscle mass and increase in body fat, the deterioration in renal and hepatic function, the plasma clearance and the volume of distribution in elderly are smaller. These changes can be exacerbated in cancer patients. We also find modifications of the NMJ: dysfunctional mitochondria, modifications in the innervation of muscle fibers and motor units, uncoupling of the excitation-contraction of muscle fibers, inflammation. : Neuromuscular blocking agents (NMBAs) compete with acetylcholine and prevent it from fixing itself on its receptor. Many publications reported guidelines for using NMBAs in the elderly, based on studies comparing old people with young people. : No one screened frailty before, and thus, no studies compared frail elderly and non-frail elderly undergoing cancer surgery. Conclusion: Despite many studies about curarisation in the specific populations, and many arguments for a potential interest for investigation, no studies investigated specifically the response to NMBAs in regard of the frailty-induced and age-related sarcopenia.

scholarly journals A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 183
Author(s):  
Anna Izzo ◽  
Elena Massimino ◽  
Gabriele Riccardi ◽  
Giuseppe Della Pepa
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Elderly Population ◽  
The Elderly ◽  
Narrative Review ◽  
Macrovascular Complications ◽  
Diabetic Patients ◽  
Age Related

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.

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