Animal models of high-risk corneal transplantation: A comprehensive review.
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ABSTRACT:
SUBMITTER: Singh RB
PROVIDER: S-EPMC7508940 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeTo present an overview of animal models of retinal artery occlusion (RAO).MethodsThrough a systematic literature search in PubMed and Embase, papers describing methods of inducing RAO in animal models were included. The identified methodologic approaches were presented in a narrative synthesis and compared with RAO in humans.ResultsIn total, 83 papers reporting on 88 experiments were included. Six different species were used with rodents and monkeys being the most common, and a minority were performed using cats, dogs, rabbits, or pigs. The anatomy of pigs and monkeys resemble that of humans most closely. The two most frequently used methods were laser-induced occlusion or ligation of the arteries. Other methods included raised intraocular pressure, arterial clamping, administration of vasoconstricting agents, the use of an occluder, embolization, and endovascular approaches to induce occlusion. In general, occlusions lasted for only 30 to 90 minutes, often followed by reperfusion.ConclusionsAlthough a broad range of methods have previously been used, they all have limitations. Preferably, the methods should imitate the human disease as closely as possible and avoid damaging other structures. Therefore, monkeys followed by pigs are to be preferred and ligation or clamping may be a suitable model in larger animals as there is a potential to isolate and occlude the retinal artery only. Being less invasive, laser-induced occlusion is another suitable approach.Translational relevanceThis review aims at assisting researchers in deciding on the most ideal experimental setting, and thereby increase the translational value to human disease.
| S-EPMC6701503 | biostudies-literature
Project description:Emerging and re-emerging viral diseases can create devastating effects on human lives and may also lead to economic crises. The ongoing COVID-19 pandemic due to the novel coronavirus (nCoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has caused a global public health emergency. To date, the molecular mechanism of transmission of SARS-CoV-2, its clinical manifestations and pathogenesis is not completely understood. The global scientific community has intensified its efforts in understanding the biology of SARS-CoV-2 for development of vaccines and therapeutic interventions to prevent the rapid spread of the virus and to control mortality and morbidity associated with COVID-19. To understand the pathophysiology of SARS-CoV-2, appropriate animal models that mimic the biology of human SARS-CoV-2 infection are urgently needed. In this review, we outline animal models that have been used to study previous human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). Importantly, we discuss models that are appropriate for SARS-CoV-2 as well as the advantages and disadvantages of various available methods.
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Project description:Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC). Although LT eliminates HCC and greatly reduces recurrence, some patients experience recurrence after LT. Criteria and models for screening patients with a high probability of HCC recurrence after LT, starting with the Milan criteria, have been published. These models have changed over time, but a standard has not been established. We summarized HCC prediction models after LT by focusing on the application of radiologic, serologic, and pathologic factors and recent trends. This review will look at studies that are based on living donor LT and deceased donor LT, as well as studies that downstaging procedures have been performed preoperatively. This ultimately aims to help make decisions for evaluating the HCC state and selecting candidates for LT according to the circumstances of each transplantation center.
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Project description:GSD are a group of disorders characterized by a defect in gene expression of specific enzymes involved in glycogen breakdown or synthesis, commonly resulting in the accumulation of glycogen in various tissues (primarily the liver and skeletal muscle). Several different GSD animal models have been found to naturally present spontaneous mutations and others have been developed and characterized in order to further understand the physiopathology of these diseases and as a useful tool to evaluate potential therapeutic strategies. In the present work we have reviewed a total of 42 different animal models of GSD, including 26 genetically modified mouse models, 15 naturally occurring models (encompassing quails, cats, dogs, sheep, cattle and horses), and one genetically modified zebrafish model. To our knowledge, this is the most complete list of GSD animal models ever reviewed. Importantly, when all these animal models are analyzed together, we can observe some common traits, as well as model specific differences, that would be overlooked if each model was only studied in the context of a given GSD.
| S-EPMC7766110 | biostudies-literature
Project description:PurposeTo determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation.DesignPilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil.ParticipantsPatients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft.MethodsPatients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks.Main outcome measureThe 52-week endothelial immune rejection rate.ResultsNinety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis.ConclusionsIn patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.
| S-EPMC10742165 | biostudies-literature
Project description:The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and recipient animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the animal model which is used. METHODS:In this study, we systematically identified all publications concerning transplantation of RPE in experimental animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a- and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays. RESULTS:original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; n = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave (Hedges' g 1.181 (0.471-1.892), n = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), n = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), n = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent animals compared to adult animals. Moreover, transplanting more cells (in the range of 105 versus in the range of 104) resulted in a significantly increased effect on vision-based behavior as well. The origin of cells mattered as well. A significantly increased effect was found on vision-based behavior when using ARPE-19 and OpRegen® RPE. CONCLUSIONS:This systematic review shows that RPE transplantation in animal models for retinal degeneration significantly increases a- and b- wave amplitudes and improves vision-related behavior. These effects appear to be more pronounced in young animals, when the number of transplanted cells is larger and when ARPE-19 and OpRegen® RPE cells are used. We further emphasize that there is an urgent need for improving the reporting and methodological quality of animal experiments, to make such studies more comparable.
| S-EPMC7216090 | biostudies-literature
Project description:Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds. Treatment of donor corneas with interleukin-10 (IL-10) and transforming growth factor-β1 (TGFβ1) altered the phenotype and function of tissue-residing APCs. Transplantation of these tolAPC-enriched corneas decreased frequencies of interferon gamma (IFNγ)+ effector T cells (Teffs), as well as allosensitization in the hosts, diminished graft infiltration of CD45+ and CD4+ cells, and significantly improved corneal allograft survival compared to saline-injected controls. These data provide a novel approach for tolAPC-based immunotherapy in transplantation by direct cytokine conditioning of the donor tissue.
| S-EPMC5430534 | biostudies-literature
Project description:The need for alternative treatments for multiple sclerosis (MS) has triggered copious amounts of research into microbial therapies focused on manipulating the microbiota-gut-brain axis. This comprehensive review was intended to present and systematically evaluate the current clinical and preclinical evidence for various probiotic and commensal gut microbial therapies as treatments for MS, using the Bradford Hill criteria (BHC) as a multi-parameter assessment rubric. Literature searches were performed to identify a total of 37 relevant studies (6 human, 31 animal), including 28 probiotic therapy and 9 commensal therapy studies. In addition to presenting qualitative summaries of these findings, therapeutic evidence for each bacterial formulation was assessed using the BHC to generate summative scores. These scores, which encompassed study quality, replication, and other considerations, were used to rank the most promising therapies and highlight deficiencies. Several therapeutic formulations, including VSL#3, Lactobacillus paracasei, Bifidobacterium animalis, E. coli Nissle 1917, and Prevotella histicola, emerged as the most promising. In contrast, a number of other therapies were hindered by limited evidence of replicable findings and other criteria, which need to be addressed by future studies in order to harness gut microbial therapies to ultimately provide cheaper, safer, and more durable treatments for MS.
| S-EPMC8284149 | biostudies-literature
Project description:BackgroundTo mimic systemic inflammation in humans, different animal models have been developed. Since these models are still discussed controversially, we aimed to comparatively evaluate the most widely used models with respect to the systemic effects, the influence on organ functions and to the underlying pathophysiological processes.MethodsSystemic inflammation was induced in C57BL/6N mice with lipopolysaccharide (LPS) treatment, peritoneal contamination and infection (PCI), or cecal ligation and puncture (CLP). Blood glucose and circulating cytokine levels were evaluated at 0, 2, 4, 6, 12, 24, 48, and 72 h after induction of inflammation. Additionally, oxidative stress in various organs and liver biotransformation capacity were determined. Markers for oxidative stress, apoptosis, infiltrating immune cells, as well as cytokine expression patterns, were assessed in liver and spleen tissue by immunohistochemistry.ResultsTreating mice with LPS and PCI induced a very similar course of inflammation; however, LPS treatment elicited a stronger response. In both models, serum pro-inflammatory cytokine levels rapidly increased whereas blood glucose decreased. Organs showed early signs of oxidative stress, and apoptosis was increased in splenic cells. In addition, liver biotransformation capacity was reduced and there was pronounced immune cell infiltration in both the liver and spleen. Mice exposed to either LPS or PCI recovered after 72 h. In contrast, CLP treatment induced comparatively fewer effects, but a more protracted course of inflammation.ConclusionsThe LPS model of systemic inflammation revealed to be most suitable when being interested in the impact of new therapies for acute inflammation. When using the CLP model to mimic human sepsis more closely, a longer time course should be employed, as the treatment induces delayed development of systemic inflammation.
| S-EPMC5569462 | biostudies-literature
Project description:To date, few studies have focused on the characterization of clinical phenomenology regarding gender in population at high-risk of psychosis. This paper is an attempt to summarize the findings found in the scientific literature regarding gender differences in high-risk populations, taking into account parameters studied in populations with schizophrenia and other psychotic disorders, such as incidence, clinical expression, duration of untreated illness (DUI), social functioning, and cognitive impairment prior to full-blown psychosis development.Studies were systematically searched in PubMed. Studies using gender variable as a control variable were excluded. 12 studies met inclusion criteria.Most of the studies found a differential pattern between women and men as regards clinical, social, and cognitive variables in the prodromal phase, with worse performance in men except in cognitive functioning (more severe negative symptoms, worse social functioning, and longer DUI in men). Similar conversion rates over time were found between men and women.Many of the studies analyzed suggest that differences between men and women in the expression of psychosis extend across a continuum, from the subclinical forms of illness to the debut of psychosis. However, the small number of studies and their significant methodological and clinical limitations do not allow for firm conclusions.
| S-EPMC4312997 | biostudies-other