scholarly journals Cone photoreceptor reflectance variation in the northern tree shrew and thirteen-lined ground squirrel

2021 ◽  
pp. 153537022110295
Author(s):  
Mina Gaffney ◽  
Robert F Cooper ◽  
Jenna A Cava ◽  
Hannah M Follett ◽  
Alexander E Salmon ◽  
...  
Keyword(s):  
Animal Models ◽  
Adaptive Optics ◽  
Ground Squirrel ◽  
Light Propagation ◽  
Ex Vivo ◽  
Tree Shrew ◽  
Theoretical Models ◽  
Cone Photoreceptors ◽  
Cone Structure

In vivo images of human cone photoreceptors have been shown to vary in their reflectance both spatially and temporally. While it is generally accepted that the unique anatomy and physiology of the photoreceptors themselves drives this behavior, the exact mechanisms have not been fully elucidated as most studies on these phenomena have been limited to the human retina. Unlike humans, animal models offer the ability to experimentally manipulate the retina and perform direct in vivo and ex vivo comparisons. The thirteen-lined ground squirrel and northern tree shrew are two emerging animal models being used in vision research. Both models feature cone-dominant retinas, overcoming a key limitation of traditional rodent models. Additionally, each possesses unique but well-documented anatomical differences in cone structure compared to human cones, which can be leveraged to further constrain theoretical models of light propagation within photoreceptors. Here we sought to characterize the spatial and temporal reflectance behavior of cones in these species. Adaptive optics scanning light ophthalmoscopy (AOSLO) was used to non-invasively image the photoreceptors of both species at 5 to 10 min intervals over the span of 18 to 25 min. The reflectance of individual cone photoreceptors was measured over time, and images at individual time points were used to assess the variability of cone reflectance across the cone mosaic. Variability in spatial and temporal photoreceptor reflectance was observed in both species, with similar behavior to that seen in human AOSLO images. Despite the unique cone structure in these animals, these data suggest a common origin of photoreceptor reflectance behavior across species. Such data may help constrain models of the cellular origins of photoreceptor reflectance signals. These animal models provide an experimental platform to further explore the morphological origins of light capture and propagation.

scholarly journals Retinoid isomerase inhibitors impair but do not block mammalian cone photoreceptor function

2018 ◽  
Vol 150 (4) ◽  
pp. 571-590 ◽  
Author(s):  
Philip D. Kiser ◽  
Jianye Zhang ◽  
Aditya Sharma ◽  
Juan M. Angueyra ◽  
Alexander V. Kolesnikov ◽  
...  
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Pigment Epithelium ◽  
Light Sensitivity ◽  
Ground Squirrels ◽  
Slow Phase ◽  
Acute Administration ◽  
Visual Cycle ◽  
Cone Photoreceptors

Visual function in vertebrates critically depends on the continuous regeneration of visual pigments in rod and cone photoreceptors. RPE65 is a well-established retinoid isomerase in the pigment epithelium that regenerates rhodopsin during the rod visual cycle; however, its contribution to the regeneration of cone pigments remains obscure. In this study, we use potent and selective RPE65 inhibitors in rod- and cone-dominant animal models to discern the role of this enzyme in cone-mediated vision. We confirm that retinylamine and emixustat-family compounds selectively inhibit RPE65 over DES1, the putative retinoid isomerase of the intraretinal visual cycle. In vivo and ex vivo electroretinography experiments in Gnat1−/− mice demonstrate that acute administration of RPE65 inhibitors after a bleach suppresses the late, slow phase of cone dark adaptation without affecting the initial rapid portion, which reflects intraretinal visual cycle function. Acute administration of these compounds does not affect the light sensitivity of cone photoreceptors in mice during extended exposure to background light, but does slow all phases of subsequent dark recovery. We also show that cone function is only partially suppressed in cone-dominant ground squirrels and wild-type mice by multiday administration of an RPE65 inhibitor despite profound blockade of RPE65 activity. Complementary experiments in these animal models using the DES1 inhibitor fenretinide show more modest effects on cone recovery. Collectively, these studies demonstrate a role for continuous RPE65 activity in mammalian cone pigment regeneration and provide further evidence for RPE65-independent regeneration mechanisms.

scholarly journals An Ex Vivo Vessel Injury Model to Study Remodeling

2018 ◽  
Vol 27 (9) ◽  
pp. 1375-1389 ◽  
Author(s):  
Mehmet H. Kural ◽  
Guohao Dai ◽  
Laura E. Niklason ◽  
Liqiong Gui
Keyword(s):  
Shear Stress ◽  
Animal Models ◽  
Intimal Hyperplasia ◽  
Vascular Remodeling ◽  
Ex Vivo ◽  
Vessel Injury ◽  
Injury Model ◽  
Human Arteries

Objective: Invasive coronary interventions can fail due to intimal hyperplasia and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating re-endothelialization, or local release of mTOR pathway inhibitors have helped reduce intimal hyperplasia after vessel injury. While animal models are powerful tools, they are complex and expensive, and not always reflective of human physiology. Therefore, we developed an in vitro 3D vascular model validating previous in vivo animal models and utilizing isolated human arteries to study vascular remodeling after injury. Approach: We utilized a bioreactor that enables the control of intramural pressure and shear stress in vessel conduits to investigate the vascular response in both rat and human arteries to intraluminal injury. Results: Culturing rat aorta segments in vitro, we show that vigorous removal of luminal ECs results in vessel injury, causing medial proliferation by Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when endothelial-denuded rat aortae and human umbilical arteries were subjected to arterial shear stress, pre-seeding with human umbilical ECs decreased the number and proliferation of smooth muscle cell (SMC) significantly in the media of both rat and human vessels. Conclusion: Our bioreactor system provides a novel platform for correlating ex vivo findings with vascular outcomes in vivo. The present in vitro human arterial injury model can be helpful in the study of EC-SMC interactions and vascular remodeling, by allowing for the separation of mechanical, cellular, and soluble factors.

scholarly journals Consequences of mitral valve prolapse on chordal tension: Ex vivo and in vivo studies in large animal models

2011 ◽  
Vol 142 (6) ◽  
pp. 1585-1587 ◽  
Author(s):  
Mathieu Granier ◽  
Morten O. Jensen ◽  
Jesper L. Honge ◽  
Alain Bel ◽  
Philippe Menasché ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Animal Models ◽  
Mitral Valve Prolapse ◽  
Ex Vivo ◽  
In Vivo Studies ◽  
Large Animal ◽  
Large Animal Models

Transduodenal–transpapillary endopancreatic surgery with a rigid resectoscope: experiments on ex vivo, in vivo animal models and human cadavers

2017 ◽  
Vol 31 (10) ◽  
pp. 4131-4135 ◽  
Author(s):  
Philip C. Müller ◽  
Daniel C. Steinemann ◽  
Felix Nickel ◽  
Lukas Chinczewski ◽  
Beat P. Müller-Stich ◽  
...  
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Human Cadavers ◽  
In Vivo Animal Models

scholarly journals Neuronal Replacement in Stem Cell Therapy for Stroke: Filling the Gap

2021 ◽  
Vol 9 ◽  
Author(s):  
Sara Palma-Tortosa ◽  
Berta Coll-San Martin ◽  
Zaal Kokaia ◽  
Daniel Tornero
Keyword(s):  
Stem Cell ◽  
Animal Models ◽  
Cell Therapy ◽  
Human Skin ◽  
Stem Cell Therapy ◽  
Ex Vivo ◽  
Functional Integration ◽  
Short Review ◽  
Neuronal Replacement

Stem cell therapy using human skin-derived neural precursors holds much promise for the treatment of stroke patients. Two main mechanisms have been proposed to give rise to the improved recovery in animal models of stroke after transplantation of these cells. First, the so called by-stander effect, which could modulate the environment during early phases after brain tissue damage, resulting in moderate improvements in the outcome of the insult. Second, the neuronal replacement and functional integration of grafted cells into the impaired brain circuitry, which will result in optimum long-term structural and functional repair. Recently developed sophisticated research tools like optogenetic control of neuronal activity and rabies virus monosynaptic tracing, among others, have made it possible to provide solid evidence about the functional integration of grafted cells and its contribution to improved recovery in animal models of brain damage. Moreover, previous clinical trials in patients with Parkinson’s Disease represent a proof of principle that stem cell-based neuronal replacement could work in humans. Our studies with in vivo and ex vivo transplantation of human skin-derived cells neurons in animal model of stroke and organotypic cultures of adult human cortex, respectively, also support the hypothesis that human somatic cells reprogrammed into neurons can get integrated in the human lesioned neuronal circuitry. In the present short review, we summarized our data and recent studies from other groups supporting the above hypothesis and opening new avenues for development of the future clinical applications.

scholarly journals Predictive Value of Precision-Cut Kidney Slices as an Ex Vivo Screening Platform for Therapeutics in Human Renal Fibrosis

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 459 ◽  
Author(s):  
Emilia Bigaeva ◽  
Nataly Puerta Cavanzo ◽  
Elisabeth G. D. Stribos ◽  
Amos J. de Jong ◽  
Carin Biel ◽  
...  
Keyword(s):  
Animal Models ◽  
Renal Fibrosis ◽  
Ex Vivo ◽  
Collagen Type I ◽  
Type I ◽  
Preclinical Research ◽  
Predictive Tool ◽  
Predictive Capacity ◽  
Kidney Slices

Animal models are a valuable tool in preclinical research. However, limited predictivity of human biological responses in the conventional models has stimulated the search for reliable preclinical tools that show translational robustness. Here, we used precision-cut kidney slices (PCKS) as a model of renal fibrosis and investigated its predictive capacity for screening the effects of anti-fibrotics. Murine and human PCKS were exposed to TGFβ or PDGF pathway inhibitors with established anti-fibrotic efficacy. For each treatment modality, we evaluated whether it affected: (1) culture-induced collagen type I gene expression and interstitial accumulation; (2) expression of markers of TGFβ and PDGF signaling; and (3) expression of inflammatory markers. We summarized the outcomes of published in vivo animal and human studies testing the three inhibitors in renal fibrosis, and drew a parallel to the PCKS data. We showed that the responses of murine PCKS to anti-fibrotics highly corresponded with the known in vivo responses observed in various animal models of renal fibrosis. Moreover, our results suggested that human PCKS can be used to predict drug efficacy in clinical trials. In conclusion, our study demonstrated that the PCKS model is a powerful predictive tool for ex vivo screening of putative drugs for renal fibrosis.

scholarly journals Imaging pheochromocytoma in small animals: preclinical models to improve diagnosis and treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hermine Mohr ◽  
Alessia Foscarini ◽  
Katja Steiger ◽  
Simone Ballke ◽  
Christoph Rischpler ◽  
...  
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Therapy Response ◽  
Human Cell Line ◽  
Mouse Cell ◽  
Cardiovascular Complications ◽  
Imaging Modalities ◽  
Life Threatening ◽  
Early Tumor

AbstractPheochromocytomas (PCCs) and paragangliomas (PGLs), together referred to as PPGLs, are rare chromaffin cell-derived tumors. They require timely diagnosis as this is the only way to achieve a cure through surgery and because of the potentially serious cardiovascular complications and sometimes life-threatening comorbidities that can occur if left untreated. The biochemical diagnosis of PPGLs has improved over the last decades, and the knowledge of the underlying genetics has dramatically increased. In addition to conventional anatomical imaging by CT and MRI for PPGL detection, new functional imaging modalities have emerged as very useful for patient surveillance and stratification for therapy. The availability of validated and predictive animal models of cancer is essential for translating molecular, imaging and therapy response findings from the bench to the bedside. This is especially true for rare tumors, such as PPGLs, for which access to large cohorts of patients is limited. There are few animal models of PPGLs that have been instrumental in refining imaging modalities for early tumor detection, as well as in identifying and evaluating novel imaging tracers holding promise for the detection and/or treatment of human PPGLs. The in vivo PPGL models mainly include xenografts/allografts generated by engrafting rat or mouse cell lines, as no representative human cell line is available. In addition, there is a model of endogenous PCCs (i.e., MENX rats) that was characterized in our laboratory. In this review, we will summarize the contribution that various representative models of PPGL have given to the visualization of these tumors in vivo and we present an example of a tracer first evaluated in MENX rats, and then translated to the detection of these tumors in human patients. In addition, we will illustrate briefly the potential of ex vivo biological imaging of intact adrenal glands in MENX rats.

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