Use Of Experimental Models Research Articles

Comparative assessment of FSM and MPSIAC models in quantifying soil sedimentation rates in the semi-humid and alpine regions of northern Iran.

Soil erosion and sediment yield is a global problem that increasingly contributes to soil degradation. Although erosion analysis requires the availability of erosion and sedimentation data, the lack of sediment monitoring stations and the resulting limitations in collecting sediment measurements have necessitated the use of experimental models in many areas. The present study aimed to compare Factorial Scoring Model (FSM) and Modified Pacific South-West Inter-Agency Committee (MPSIAC) model for estimating erosion in the Mazdaran Basin (Firoozkuh, Iran). For this purpose, the required maps were prepared for both models, and the sediment rate was estimated using the two models to compare their efficiency using the corresponding maximum error (ME) and coefficient of determination (R2) values. The results showed that considering sediment based on the FSM model, the studied catchment consisted of regions with a high and very high sediment yield, while the MPSIAC model identified regions with low, medium, and high sediment yield. With an R2 value of 0.62 and an ME value of 2.24, the MPSIAC model provided more accurate estimates of the sediment yield in the studied area. Using the MPSIAC model, sediment yield was 6687.86 tons per year or the equivalent of 2.64 tons/ha per year.

The Effect of Chronic Levetiracetam Use on Erythrocyte Deformability

ABSTRACT Background: The inhibition of carbonic anhydrase (CA) isoenzymes is one of the targets in the development of new antiepileptics. Levetiracetam (LEV) is a new-generation antiepileptic drug frequently used in pediatric patients. It has a strong inhibitory effect on CA enzymes in many tissues, including erythrocytes. Objective: Due to CA enzymes have physical connection with the erythrocyte membrane and cytoskeleton, we aimed to evaluate the probable effect of LEV on the erythrocyte deformability. Materials and Methods: This study was conducted in the Experimental Animal Laboratory of Ankara Training and Research Hospital 24 prepubertal female Wistar albino rats were divided into four groups with six animals in each group. Group I: Control (distilled water), Group II: LEV50 (50 mg/kg/day), Group III: LEV150 (150 mg/kg/day), Group IV: LEV300 (300 mg/kg/day). The calculated dose for each animal was given by oral gavage once a day for 14 days, which is accepted as chronic use in experimental models. At the end of the treatment period, erythrocyte deformability was evaluated both with whole blood viscosity at high shear rates, and osmotic fragility test. Results: No statistically significant difference was found between the groups in terms of osmotic fragility. Whole blood and plasma viscosity values also did not show any statistically significant difference between the groups. Conclusion: In this study, it has been shown that LEV does not have a negative effect on erythrocyte deformability. Therefore, we thought that it may be a good choice when an antiepileptic is needed in pediatric patients with hematological disorders.

Does retinal microglia respond to peripheral nervous system injury?

The nervous system is the principal integration and coordination centre of the organism receiving, processing and transmitting information to produce a response that regulates and maintains homeostasis. In the central nervous system (CNS), homeostasis is regulated by haemato‐neuronal barriers that prevent free entry to immune system cells, although there is increasing evidence that neuro‐immunological interactions during injury, inflammation and chronic peripheral disease may contribute to the establishment and development of chronic neurodegenerative pathologies at the CNS level.Inflammation plays a significant role in the resolution and sequelae of CNS damage. In recent years, special attention has been dedicated to the role and phenotype of phagocytic cells acting in the CNS and, in particular, to the study of which macrophage subpopulations contribute to excessive or detrimental inflammation or, on the contrary, to beneficial repair or resolution of the lesion.All this raises the question of how local peripheral neuroimmunological interaction induces an inflammatory response in the CNS and how this can be better understood. The study of this phenomenon in the retina is of particular interest, as the retina does not receive neural afferents from other areas of the CNS.The use of experimental models of peripheral lesions of the peripheral nervous system, such as sciatic nerve trauma, or inflammatory lesions, such as the induction of a peripheral arthritic joint process, aims to investigate the time course of the response in the CNS to local peripheral inflammation in the retina of adult mice. The results reveal qualitative and quantitative cellular changes compatible with microglial activation processes in the retina, but no significant changes occur in its neuronal population. The presence and activation of haematic mononuclear‐phagocytic cells of myelopoietic origin are also observed in the retina, where they differentiate into microglia.In the absence of local retinal injury, we postulate that the detected neuroinflammatory reaction may be due to a preventive CNS defence reaction favouring neuroprotection since microglial cells derived from the haematic monocyte/macrophage cell population may consider within the M2 macrophage subtype, characterized by their ability to suppress proinflammatory immune responses and promote the expression of neuroprotective and repair genes.On the other hand, we must consider that activation of the mononuclear phagocytic system in the retina caused by a peripheral inflammatory process could potentially be detrimental to patients with neurodegenerative retinal diseases or contribute to their development.

Non-Coding RNAs Regulate Spinal Cord Injury-Related Neuropathic Pain via Neuroinflammation.

Secondary chronic neuropathic pain (NP) in addition to sensory, motor, or autonomic dysfunction can significantly reduce quality of life after spinal cord injury (SCI). The mechanisms of SCI-related NP have been studied in clinical trials and with the use of experimental models. However, in developing new treatment strategies for SCI patients, NP poses new challenges. The inflammatory response following SCI promotes the development of NP. Previous studies suggest that reducing neuroinflammation following SCI can improve NP-related behaviors. Intensive studies of the roles of non-coding RNAs in SCI have discovered that ncRNAs bind target mRNA, act between activated glia, neuronal cells, or other immunocytes, regulate gene expression, inhibit inflammation, and influence the prognosis of NP.

Modeling Central Nervous System Injury In Vitro: Current Status and Promising Future Strategies.

The central nervous system (CNS) injury, which occurs because of mechanical trauma or ischemia/hypoxia, is one of the main causes of mortality and morbidity in the modern society. Until know, despite the fact that numerous preclinical and clinical studies have been undertaken, no significant neuroprotective strategies have been discovered that could be used in the brain trauma or ischemia treatment. Although there are many potential explanations for the failure of those studies, it is clear that there are questions regarding the use of experimental models, both in vivo and in vitro, when studying CNS injury and searching new therapeutics. Due to some ethical issues with the use of live animals in biomedical research, implementation of experimental strategies that prioritize the use of cells and tissues in the in vitro environment has been encouraged. In this review, we examined some of the most commonly used in vitro models and the most frequently utilized cellular platforms in the research of traumatic brain injury and cerebral ischemia. We also proposed some future strategies that could improve the usefulness of these studies for better bench-to-bedside translational outcomes.

Spinal Canal and Spinal Cord in Rat Continue to Grow Even after Sexual Maturation: Anatomical Study and Molecular Proposition.

Although rodents have been widely used for experimental models of spinal cord diseases, the details of the growth curves of their spinal canal and spinal cord, as well as the molecular mechanism of the growth of adult rat spinal cords remain unavailable. They are particularly important when conducting the experiments of cervical spondylotic myelopathy (CSM), since the disease condition depends on the size of the spinal canal and the spinal cord. Thus, the purposes of the present study were to obtain accurate growth curves for the spinal canal and spinal cord in rats; to define the appropriate age in weeks for their use as a CSM model; and to propose a molecular mechanism of the growth of the adult spinal cord in rats. CT myelography was performed on Lewis rats from 4 weeks to 40 weeks of age. The vertical growth of the spinal canal at C5 reached a plateau after 20 and 12 weeks, and at T8 after 20 and 16 weeks, in males and females, respectively. The vertical growth of the C5 and T8 spinal cord reached a plateau after 24 weeks in both sexes. The vertical space available for the cord (SAC) of C5 and T8 did not significantly change after 8 weeks in either sex. Western blot analyses showed that VEGFA, FGF2, and BDNF were highly expressed in the cervical spinal cords of 4-week-old rats, and that the expression of these growth factors declined as rats grew. These findings indicate that the spinal canal and the spinal cord in rats continue to grow even after sexual maturation and that rats need to be at least 8 weeks of age for use in experimental models of CSM. The present study, in conjunction with recent evidence, proposes the hypothetical model that the growth of rat spinal cord after the postnatal period is mediated at least in part by differentiation of neural progenitor cells and that their differentiation potency is maintained by VEGFA, FGF2, and BDNF.

Creatine supplementation to improve the peripheral and central inflammatory profile in cerebral palsy.

This opinion paper presents a brief review on the potential use of Creatine (Cr) to improve the inflammatory profile in individuals with Cerebral Palsy (CP). CP is a condition that causes muscle atrophy followed by reduced strength and altered muscle tone. The prevalence of chronic diseases is higher in people with CP due to this, which are often associated with peripheral inflammation, but there are no studies that have evaluated central inflammation in this condition. Nevertheless, the anti-inflammatory action of Cr has already been observed in different types of studies. Thus, the use of experimental models of CP to evaluate the expression of the inflammatory markers, especially in the brain, as well as approaches to reduce the impairments already observed becomes essential. Results obtained in these preclinical studies may contribute to the quality of therapeutic strategies offered to children suffering from CP, the most common cause of chronic motor disability in childhood.

Standardization and Ameliorative effect of Kalyanaka ghrita in β-amyloid induced memory impairment in wistar rats

Ethnopharmacological relevanceKalyanaka ghrita (KG) is an Ayurvedic formulation traditionally used in the treatment of Daurbalya (debility) and Smritidaurbalya (impairment of intellectual activities). Clinical studies have reported the effect of KG in the treatment of Manasmandata or Buddhimandyata which is associated with impaired learning, social adjustment and maturation. Aim of the studyThe present study aims to standardization of KG and validation of its use in experimental models of neurodegeneration. Materials and methodsKG was Standardized for biomarkers curcumin, gallic acid, tannic acid, chebulagic acid, and berberine. In male wistar rats, neurodegeneration was induced by administration of intracerebroventricular Amyloid β (Aβ1-42). The effect of KG (oral and intranasal treatment) was evaluated through behavioral parameters such as Morris water maze, social recognition test, novel object recognition, locomotor activity, and molecular parameters, brain acetylcholinesterase, brain-derived neurotrophic factor (BDNF), inflammatory cytokines, oxidative stress markers, and antioxidants. Brain histopathology was performed for studying the architecture of the brain and plaque formation. Results and discussionA novel HPLC method has been developed for the standardization of KG. Treatment with KG significantly improved cognition and memory and increased brain BDNF and antioxidant status in Aβ1-42 induced rats. It also reduced brain acetylcholinesterase, oxidative stress, and inflammatory cytokines and prevented neuronal damage. There were more marked effects with intra-nasal administration compared to oral treatment. ConclusionThe findings suggest that KG has neuroprotective potential and along with its nootropic property could be a promising therapy for neurodegenerative diseases like Alzheimer's disease.

Morphological and morphometric study of the superior vestibular nerve trunk in guinea pigs.

The guinea pig has been chosen as a research model for otologic or neuropathic studies due to the relative ease of the cochlea, cochlear nerve, and vestibular nerve dissection. Little data have been reported on the normality of these nerves. The vestibular nerve is composed of the superior vestibular, inferior vestibular, and branch nerves. This study aimed to study the microscopic anatomy of the superior vestibular nerve (SVN) of guinea pigs using light microscopy and to search for normality patterns for use in experimental models in basic otologic research. We used eight male albino guinea pigs (Cavia porcellus, English strain), weighing between 400 and 500 g. After anesthetizing, the animals were perfused with a fixative solution of 2.5% glutaraldehyde. Dissection was performed by the access method to the temporal bone, coming to the rock and exposing the cochlea and vestibular nerve. The NVS fragments were removed, postfixed in osmium tetroxide, and embedded in the epoxy plastic resin Poly/Bed 812® (Polysciences Inc., Warrington, PA). Semi-thin transverse serial sections (0.5μm) were made using a microtome MT6000-XL, RMC, Inc. and stained with toluidine blue. Morphology and morphometry were described and evaluated using the KS 400 application (Kontron 2.0, EchingBei, Munich, Germany) by macro, a computer program specially designed and developed for the study of the VIII nerve. The SVN was found to be devoid of epineurium, with only a thin conjunctive tissue layer. The myelin sheath of guinea pigs is relatively thin compared to the sensory and motor nerves found in mammals. The average fascicular area SVN was 0.19 ± 0.05 mm2 , with the largest area found to be 0.24 mm2 and the lowest was 0.12 mm2 . The average number of fibers was 5,753.00 ± 538 fibers. The density of myelinated fibers reached 32,316.08 ± 11,375.29 fibers/mm2 . Its diameter ranged from 1.0 to 9μm and its peak was 3μm. The measured results confirm the results of another study, indicating that the methodology is appropriate and reproducible. These findings are important for the evaluation of injured nerves in experimental models of peripheral neuropathy and basic ear disease.

Abstract P3037: Metabolic Transitions In The Developing Mouse Heart

During cardiac development, cellular energy production evolves dramatically. Mechanisms that control these changes and activation of electron transport chain (ETC) remain unclear. Our aim was to provide a comprehensive analysis of mitochondrial biology and bioenergetics in the developing wild type heart for use in experimental models, such as mice, in which the mitochondrial protein, cyclophilin D (CyPD), was deleted. Mouse hearts were harvested from wild type and CyPD null hearts throughout development and examined by electron microscopy, liquid chromatography/mass spectrometry, oxygen consumption and enzyme assays, gel electrophoresis/immunoblotting, and calcium retention capacity (CRC). As the heart develops, myocyte size and mitochondrial number, size, and complexity increases with transitions at the end of the embryonic period and immediately after birth. Metabolomic profiling demonstrated changes in glycolysis, the TCA cycle, and redox state during development and these changes may facilitate proliferation in the neonatal heart. Activation of ETC complexes I, III, IV, and V occurs in the mid-embryonic period, while assembly of ETC supercomplexes begins at the late embryonic period. In contrast, complex II activity is relatively stable during development. CRC assays demonstrated a gradual decrease in the probability of mPTP opening during development, and while CyPD expression increased, its specific enzymatic activity decreased. For most assays tested, these metabolic transitions occurred earlier in development in CyPD null mice. In conclusion, the developing heart undergoes changes in cellular bioenergetics with two transitions at the end of the embryonic period and immediately after birth. Deletion of CyPD causes these transitions to occur earlier in development, suggesting that CyPD and closure of the mPTP controls mitochondrial activation and bioenergetics during cardiac development.

Understanding the pathogenesis of occupational coal and silica dust-associated lung disease.

Workers in the mining and construction industries are at increased risk of respiratory and other diseases as a result of being exposed to harmful levels of airborne particulate matter (PM) for extended periods of time. While clear links have been established between PM exposure and the development of occupational lung disease, the mechanisms are still poorly understood. A greater understanding of how exposures to different levels and types of PM encountered in mining and construction workplaces affect pathophysiological processes in the airways and lungs and result in different forms of occupational lung disease is urgently required. Such information is needed to inform safe exposure limits and monitoring guidelines for different types of PM and development of biomarkers for earlier disease diagnosis. Suspended particles with a 50% cut-off aerodynamic diameter of 10 µm and 2.5 µm are considered biologically active owing to their ability to bypass the upper respiratory tract's defences and penetrate deep into the lung parenchyma, where they induce potentially irreversible damage, impair lung function and reduce the quality of life. Here we review the current understanding of occupational respiratory diseases, including coal worker pneumoconiosis and silicosis, and how PM exposure may affect pathophysiological responses in the airways and lungs. We also highlight the use of experimental models for better understanding these mechanisms of pathogenesis. We outline the urgency for revised dust control strategies, and the need for evidence-based identification of safe level exposures using clinical and experimental studies to better protect workers' health.

Policy Focus: Building a better picture of the current use of experimental models for human and animal research

Policy Focus: Building a better picture of the current use of experimental models for human and animal research

Coagulopathy induced by viperid snake venoms in a murine model: Comparison of standard coagulation tests and rotational thromboelastometry

Viperid snakebite envenoming is often characterized by a venom-induced consumption coagulopathy due to the procoagulant effect of venom components, resulting in the alteration of clotting laboratory tests. There is a growing trend to use rotational thromboelastometry in the assessment of clotting disturbances in a variety of pathologies, although its use in experimental models of envenoming has been limited. An in vivo murine model was implemented to assess the coagulopathy induced by three Central American viperid venoms which have different mechanisms of action on clotting factors, i.e., Bothrops asper, Crotalus simus and Bothriechis lateralis. Venom was injected by the intravenous route and blood samples were collected at 1, 3, 5 and 24 h after envenoming. Coagulopathy was assessed by standard clotting tests and by routine rotational thromboelastometric parameters. In addition, the changes in platelet number were followed. B. asper and C. simus venoms induced coagulopathy and thrombocytopenia 1 h after injection, followed by a slow recovery at 3, 5 and 24 h, although the majority of clotting parameters were still significantly affected by 3 and 5 h, and were corrected by 24 h. In general, a similar time-course of alterations was observed for standard clotting tests and most rotational thromboelastomeric assays. However, some thromboelastometric parameters, especially those related to Fibtem, showed more drastic alterations than standard tests and remained altered even at 24 h in some cases. This is likely related to the low fibrinogen concentration observed at most time intervals. B. lateralis venom did not induce a consumption coagulopathy, although it caused a marked thrombocytopenia.

Possible kidney-lung cross-talk in COVID-19: in silico modeling of SARS-CoV-2 infection

BackgroundPublicly available genomics datasets have grown drastically during the past decades. Although most of these datasets were initially generated to answer a pre-defined scientific question, their repurposing can be useful when new challenges such as COVID-19 arise. While the establishment and use of experimental models of COVID-19 are in progress, the potential hypotheses for mechanisms of onset and progression of COVID-19 can be generated by using in silico analysis of known molecular changes during COVID-19 and targets for SARS-CoV-2 invasion.MethodsSelecting condition: COVID-19 infection leads to pneumonia and mechanical ventilation (PMV) and associated with acute kidney injury (AKI). There is increasing data demonstrating mechanistic links between AKI and lung injury caused by mechanical ventilation.Selecting targets: SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) for cell entry. We hypothesized that expression of ACE2 and TMPRSS2 would be affected in models of AKI and PMV. We therefore evaluated expression of ACE2 and TMPRSS2 as well as other novel molecular players of AKI and AKI-lung cross-talk in the publicly available microarray datasets GSE6730 and GSE60088, which represent gene expression of lungs and kidneys in mouse models of AKI and PMV, respectively.ResultsExpression of COVID-19 related genes ACE2 and TMPRSS2 was downregulated in lungs after 6 h of distant AKI effects. The expression of ACE2 decreased further after 36 h, while expression of TMPRSS2 recovered. In kidneys, both genes were downregulated by AKI, but not by distant lung injury. We also identified 53 kidney genes upregulated by PMV; and 254 lung genes upregulated by AKI, 9 genes of which were common to both organs. 3 of 9 genes were previously linked to kidney-lung cross-talk: Lcn2 (Fold Change (FC)Lung (L) = 18.6, FCKidney (K) = 6.32), Socs3 (FCL = 10.5, FCK = 10.4), Inhbb (FCL = 6.20, FCK = 6.17). This finding validates the current approach and reveals 6 new candidates, including Maff (FCL = 7.21, FCK = 5.98).ConclusionsUsing our in silico approach, we identified changes in COVID-19 related genes ACE2 and TMPRSS2 in traditional mouse models of AKI and kidney-lung cross-talk. We also found changes in new candidate genes, which could be involved in the combined kidney-lung injury during COVID-19.

Genetic and epigenetic dependencies in colorectal cancer development.

Recent studies have mapped key genetic changes in colorectal cancer (CRC) that impact important pathways contributing to the multistep models for CRC initiation and development. In parallel with genetic changes, normal and cancer tissues harbor epigenetic alterations impacting regulation of critical genes that have been shown to play profound roles in the tumor initiation. Cumulatively, these molecular changes are only loosely associated with heterogenous transcriptional programs, reflecting the heterogeneity in the various CRC molecular subtypes and the paths to CRC development. Studies from mapping molecular alterations in early CRC lesions and use of experimental models suggest that the intricate dependencies of various genetic and epigenetic hits shape the early development of CRC via different pathways and its manifestation into various CRC subtypes. We highlight the dependency of epigenetic and genetic changes in driving CRC development and discuss factors affecting epigenetic alterations over time and, by extension, risk for cancer.

Matching mouse models to specific human liver disease states by comparative functional genomics of mouse and human datasets

Omics has broadened our view of transcriptional and gene regulatory networks of multifactorial diseases, such as metabolism associated liver disease and its advanced stages including hepatocellular carcinoma. Identifying liver disease biomarkers and potential treatment targets makes use of experimental models, e.g. genetically engineered mice, which show molecular features of human pathologies but are experimentally tractable. We compared gene expression profiling data from human to our studies on transgenic mice with hepatocyte deletion of Cyp51 from cholesterol synthesis with the aim of identifying the human liver disease state best matched by the Cyp51 knockout model. Gene Expression Omnibus was used to identify relevant human datasets. We identified enriched and deregulated genes, pathways and transcription factors of mouse and human disease samples. Analysis showed a closer match of the Cyp51 knockout to the female patient samples. Importantly, CYP51 was depleted in both mouse and female human data. Among the enriched genes were the oxysterol-binding protein-related protein 3 (OSBPL3), which was enriched in all datasets, and the collagen gene COL1A2, which was enriched in both the mouse and one human dataset. KEGG and Reactome analyses revealed the most enriched pathway to be ECM-receptor interaction. Numerous transcription factors were differentially expressed in mice of both sexes and in the human female dataset, while depleted HNF4α and RXRα:PPARα-isoform1 were a hallmark in all cases. Our analysis exposed novel potential biomarkers, which may provide new avenues towards more personalized approaches and different targets in females and males. The analysis was only possible because of availability of open data resources and tools and broadly consistent annotation.

History of IgA Nephropathy Mouse Models.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

High‐fat diet and fructose drink introduced after weaning rats, induces a better human obesity model than very high‐fat diet

In the present study, we associated a high-fat diet (HF group: 45% kcal from lipids) or very high-fat (VHF group: 60% kcal from lipids) diet with a fructose drink (10% fructose) for hydration. Normal rat chow that received the control diet (content 16.3% kcal from lipid-AIN93G) and water. The treatments were introduced soon after weaning and were administered for 70days. We aimed to compare HF and VHF groups and find which acts as a better model mimicking human obesity. Body mass gain, final body weight, adipocyte area in inguinal depots, visceral and subcutaneous adipose depots, serum triacylglycerol, and VLDL-c were all higher in the HF group, followed by the VHF group, compared to the C group. Only the HF group showed hyperinsulinemia and hyperleptinemia and higher total caloric intake, Lee index, HOMA2-IR, and total cholesterol. Serum TNF-α and IL-6 levels were lower in the HF and VHF groups than in the C group at the end for 70days. In Summary, the HF (45%) diet administered with fructose induced a higher similarity of metabolic and hormonal alterations associated with human obesity. PRACTICAL APPLICATIONS: High intake of lipids with sugary drinks has been associated with obesity and its comorbidities. Although a diet with 45% or 60% of lipids is considered hyperlipidic, they are different in their effects on eating behavior and also probably from a metabolic point of view. Common sense is that the reduction in intake of lipids is favorable to health. Our study shows that this is not wholly true, and this information contributes to the guidelines for the treatment of obesity. In addition, the scientific literature on the subject has shown the most diverse results and also the use of experimental models with few similarities with human obesity. Our findings can contribute as a good model of obesity initiated during childhood to investigate possible using nutritional strategies, or the adoption of ergogenic nutritional resources in future studies, for example.

Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials.

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.

EXPERIMENTAL MODELS OF THE HYPOTHYROIDISM

Hypothyroidism is a systemic chronic disease that occurs as a result of a deficiency of thyroid hormones (thyroid hormones): triiodothyronine and tetraiodothyronine (thyroxine). Targets of thyroid hormones are almost all organs and tissues of the human body, which explains the variety of clinical manifestations that occur when these hormones are deficient. Recently, basic research through the use of experimental models has become more relevant and allowed us to obtain a number of new morphological and functional changes that occur in hypothyroidism. This review discusses the main experimental models of hypothyroidism: surgical, radioactive, dietary, anti-thyroid administration and genetics’ model. The main principle of the surgical model of hypothyroidism is to remove the thyroid gland. The radioactive model is based on the introduction of a radioactive isotope of iodine to laboratory animals. The dietary model is based on the use of a special diet with a limited amount of iodine. The drug model is based on the introduction of antithyroid drugs - methylimidazole and propylthiouracil. The principle of the genetic model consists in special genetic manipulations with the genome of laboratory animals. The advantages and disadvantages of each model are discussed. The use of sophisticated equipment has brought specialists closer to a more complete and holistic understanding of the morphological and functional manifestations of hypothyroidism. Researching of experimental models is an important tool in relation to the studying of the mechanisms underlying hypothyroidism and, as a result, in improving prevention and treatment-diagnostic strategies.