scholarly journals Tissue-Engineered Models for Glaucoma Research

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 612
Author(s):  
Renhao Lu ◽  
Paul Soden ◽  
Esak Lee

Glaucoma is a group of optic neuropathies characterized by the progressive degeneration of retinal ganglion cells (RGCs). Patients with glaucoma generally experience elevations in intraocular pressure (IOP), followed by RGC death, peripheral vision loss and eventually blindness. However, despite the substantial economic and health-related impact of glaucoma-related morbidity worldwide, the surgical and pharmacological management of glaucoma is still limited to maintaining IOP within a normal range. This is in large part because the underlying molecular and biophysical mechanisms by which glaucomatous changes occur are still unclear. In the present review article, we describe current tissue-engineered models of the intraocular space that aim to advance the state of glaucoma research. Specifically, we critically evaluate and compare both 2D and 3D-culture models of the trabecular meshwork and nerve fiber layer, both of which are key players in glaucoma pathophysiology. Finally, we point out the need for novel organ-on-a-chip models of glaucoma that functionally integrate currently available 3D models of the retina and the trabecular outflow pathway.

Author(s):  
Elizabeth L. Echalier ◽  
Prem S. Subramanian

AbstractPatients with meningiomas of the planum sphenoidale and tuberculum sella often present with insidious vision loss in one or both eyes as the only sign or symptom of their disease, although other sensory, oculomotor, and even endocrine abnormalities may be seen in a minority of cases. Incidentally discovered tumors also are common, as patients may undergo neuroimaging for unrelated symptoms or events. Depending on the size and orientation of the tumor, central vision loss from optic nerve compression may be a later sign, and loss of peripheral vision in one or both eyes may not be recognized until it has progressed to areas closer to fixation. A thorough neuroophthalmologic assessment including visual field testing will help to define the extent of optic pathway involvement. Both fundus examination and optical coherence tomography of the retinal nerve fiber layer and macular ganglion cell complex will aid in determining prognosis after treatment of the tumor. Orbital surgery rarely is indicated as primary therapy for meningiomas in this location, and surgical resection or debulking is usually pursued before consideration is given to radiation therapy. Because of the long-term risk of residual tumor growth or recurrence, neuroophthalmic surveillance along with serial neuroimaging is required for years after tumor resection and/or radiation therapy.


Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 465 ◽  
Author(s):  
Domenico Andrea Cristaldi ◽  
Azzurra Sargenti ◽  
Simone Bonetti ◽  
Francesco Musmeci ◽  
Cecilia Delprete ◽  
...  

Gathering precise information on mass density, size and weight of cells or cell aggregates, is crucial for applications in many biomedical fields with a specific focus on cancer research. Although few technical solutions have been presented for single-cell analysis, literature does not cover this aspect for 3D models such as spheroids. Since the research interest on such samples is notably rising, here we describe a flow-apparatus, and the associated physical method and operative protocol for the accurate measurements of mass density, size and weight. The technique is based on the detection of the terminal velocity of a free-falling sample into a specifically conceived analysis flow-channel. Moreover, in order to demonstrate the accuracy and precision of the presented flow-device, analyses were initially carried out on standardized polystyrene beads. Finally, to display the application of the proposed system for biological samples, mass density, size and weight of live SW620 tumor spheroids were analyzed. The combined measurements of such parameters can represent a step toward a deeper understanding of 3D culture models.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Lucie Sancey ◽  
Odile Sabido ◽  
Zhiguo He ◽  
Fabien Rossetti ◽  
Alain Guignandon ◽  
...  

Abstract Liquid deposit mimicking surface aerosolization in the airway is a promising strategy for targeting bronchopulmonary tumors with reduced doses of nanoparticle (NPs). In mimicking and studying such delivery approaches, the use of human in vitro 3D culture models can bridge the gap between 2D cell culture and small animal investigations. Here, we exposed airway epithelia to liquid-apical gadolinium-based AGuIX® NPs in order to determine their safety profile. We used a multiparametric methodology to investigate the NP’s distribution over time in both healthy and tumor-bearing 3D models. AGuIX® NPs were able to target tumor cells in the absence of specific surface functionalization, without evidence of toxicity. Finally, we validated the therapeutic potential of this hybrid theranostic AGuIX® NPs upon radiation exposure in this model. In conclusion, 3D cell cultures can efficiently mimic the normal and tumor-bearing airway epitheliums, providing an ethical and accessible model for the investigation of nebulized NPs.


Author(s):  
Ahmed Yaqinuddin ◽  
Muhammad Faisal Ikram ◽  
Ayesha Rahman Ambia ◽  
Raghad Alaujan ◽  
Junaid Kashir

AbstractAlzheimer’s disease (AD) is one of the most common causes of dementia. Disease progression is marked by cognitive decline and memory impairment due to neurodegenerative processes in the brain stemming from amyloid-β (Aβ) deposition and formation of neurofibrillary tangles. Pathogenesis in AD is dependent on two main neurological processes: formation of intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein and deposition of extracellular senile Aβ peptides. Given the nature of the disease, the pathology and progression of AD in vivo in humans have been difficult to study in vivo. To this degree, models can help to study the disease pathogenesis, biochemistry, immunological functions, genetics, and potential pharmacotherapy. While animal and two-dimensional (2D) cell culture models have facilitated significant progress in studying the disease, more recent application of novel three-dimensional (3D) culture models has exhibited several advantages. Herein, we describe a brief background of AD, and how current animal, 2D, and 3D models facilitate the study of this disease and associated therapeutics.


Biomimetics ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Aya Harb ◽  
Mohammad Fakhreddine ◽  
Hassan Zaraket ◽  
Fatima A. Saleh

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.


2019 ◽  
Vol 5 (1) ◽  
pp. 269-272
Author(s):  
Mathias Busek ◽  
Mario Schubert ◽  
Kaomei Guan ◽  
Frank Sonntag ◽  
Florian Schmieder ◽  
...  

AbstractRecently, we could demonstrate positive effects of microfluidic cultivation conditions on maturation of cardiomyocytes derived from human induced pluripotent stem cells (iPS-CMs) in a 2D model. However, 3D cell culture models are much closer to physiological conditions. Combined with microfluidics, 3D systems should resemble the in-vivo conditions even better than standard 2D cultivation. For 3D models, two main technical challenges arise, the tissue integration and sufficient nutrient supply for the cells. This work focuses on concepts for the tissue integration based on a modular approach and different manufacturing technologies as well as using an oxygenator in the microfluidic device to provide sufficient oxygen supply for the cells.


2021 ◽  
Author(s):  
Petri K.M. Purola ◽  
Janika E. Nättinen ◽  
Minna M. Parkkari ◽  
Matti U.I. Ojamo ◽  
Seppo V.P. Koskinen ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.


2021 ◽  
Vol 10 (6) ◽  
pp. 1254
Author(s):  
Warren W. Pan ◽  
Thomas W. Gardner ◽  
Jennifer L. Harder

Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models—a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual’s specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.


Author(s):  
Terry Riss ◽  
O. Joseph Trask

AbstractAlong with the increased use of more physiologically relevant three-dimensional cell culture models comes the responsibility of researchers to validate new assay methods that measure events in structures that are physically larger and more complex compared to monolayers of cells. It should not be assumed that assays designed using monolayers of cells will work for cells cultured as larger three-dimensional masses. The size and barriers for penetration of molecules through the layers of cells result in a different microenvironment for the cells in the outer layer compared to the center of three-dimensional structures. Diffusion rates for nutrients and oxygen may limit metabolic activity which is often measured as a marker for cell viability. For assays that lyse cells, the penetration of reagents to achieve uniform cell lysis must be considered. For live cell fluorescent imaging assays, the diffusion of fluorescent probes and penetration of photons of light for probe excitation and fluorescent emission must be considered. This review will provide an overview of factors to consider when implementing assays to interrogate three dimensional cell culture models.


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