Müller Cell Expression of Genes Implicated in Proliferative Vitreoretinopathy Is Influenced by Substrate Elastic Modulus

Davis, Joshua; Janmey, Paul A.; Otteson, Deborah C.; Foster, William

doi:10.1167/iovs.11-8450

Cited by 30 publications

(30 citation statements)

References 36 publications

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“…These genes are associated with proliferative vitreoretinopathy, a well-known complication that develops after retinal detachment, and were expressed in Müller cells cultured on soft substrates designed to mimic the loss of tissue stiffness found in a detached retina. 33 In our floating cultures, the phenomenon of Müller cell activation and tissue disruption was most pronounced, indicating a direct relationship between the biomechanical milieu and explant cell survival.…”

Section: Figure 6 Immunohistochemical Labeling Of Müller Cells Usingmentioning

confidence: 71%

Stretch to See: Lateral Tension Strongly Determines Cell Survival in Long-Term Cultures of Adult Porcine Retina

Taylor

Moran

Arnér

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To explore the effect of lateral tension as a survival factor for retinal explants in vitro. The central nervous system (CNS) resides in a highly mechanical milieu. However, the importance of biomechanical homeostasis for normal CNS function has not been extensively explored. Diseases in which normal mechanical forces are disrupted, such as retinal detachment of the eye, are highly debilitating and the mechanisms underlying disease progression are not fully understood.METHODS. Using a porcine animal model, we developed a novel technique of culturing adult retinal explants under stretch for up to 10 days in vitro (DIV). These were compared with standard (no stretch) and free-floating cultured explants. Cell survival was analyzed using immunohistochemistry, and retinal architecture using hematoxylin and eosin staining.RESULTS. Compared with unstretched specimens, which at 10 DIV degenerated into a gliotic cell mass, stretched retinas displayed a profound preservation of the laminar retinal architecture as well as significantly increased neuronal cell survival, with no signs of impending gliosis. CONCLUSIONS.The results confirm that biomechanical tension is a vital factor in the maintenance of retinal tissue integrity, and suggest that mechanical cues are important components of pathologic responses within the CNS. (Invest Ophthalmol Vis

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Section: Figure 6 Immunohistochemical Labeling Of Müller Cells Usingmentioning

confidence: 71%

Stretch to See: Lateral Tension Strongly Determines Cell Survival in Long-Term Cultures of Adult Porcine Retina

Taylor

Moran

Arnér

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…AFM indentation has been successfully applied for measuring the mechanical properties of a range of cell types, 25,[34][35][36] and has been used extensively for assessing changes in mechanical properties of cells associated with cellular differentiation and in various diseased contexts. 30,37 An important step to calculate stiffness from force-curve is identifying the point where the tip first makes contact with the cell. The uncertainty in contact point can affect the elastic modulus 31 .…”

Section: Discussionmentioning

confidence: 99%

“…They found that fibroblasts actively stiffen their cytoskeletons to match the stiffness of substrates they adhere to. Many other cell types have also been reported to become stiffer when cultured on stiffer substrates 30 .…”

Section: Figure 2amentioning

confidence: 99%

Measuring the Mechanical Properties of Living Cells Using Atomic Force Microscopy

Thomas

Burnham

Camesano³

et al. 2013

JoVE

Self Cite

137

127

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Mechanical properties of cells and extracellular matrix (ECM) play important roles in many biological processes including stem cell differentiation, tumor formation, and wound healing. Changes in stiffness of cells and ECM are often signs of changes in cell physiology or diseases in tissues. Hence, cell stiffness is an index to evaluate the status of cell cultures. Among the multitude of methods applied to measure the stiffness of cells and tissues, micro-indentation using an Atomic Force Microscope (AFM) provides a way to reliably measure the stiffness of living cells. This method has been widely applied to characterize the micro-scale stiffness for a variety of materials ranging from metal surfaces to soft biological tissues and cells. The basic principle of this method is to indent a cell with an AFM tip of selected geometry and measure the applied force from the bending of the AFM cantilever. Fitting the force-indentation curve to the Hertz model for the corresponding tip geometry can give quantitative measurements of material stiffness. This paper demonstrates the procedure to characterize the stiffness of living cells using AFM. Key steps including the process of AFM calibration, force-curve acquisition, and data analysis using a MATLAB routine are demonstrated. Limitations of this method are also discussed. Video LinkThe video component of this article can be found at

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“…The FNIII Domain D of TN-C is necessary to stimulate retinal outgrowth on Müller glia cells (Siddiqui et al, 2008). An increase in Müller cell proliferation has been observed on stiff substrates and an upregulation of connective tissue growth factor (CTGF) and TN-C on softer substrates (Davis et al, 2012). Recently, Müller cells were shown to have the potential to re-enter the cell cycle and differentiate into multipotent neuronal progenitors that can regenerate cells in damaged areas.…”

Section: Tenascinmentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

612

533

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The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

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Müller Cell Expression of Genes Implicated in Proliferative Vitreoretinopathy Is Influenced by Substrate Elastic Modulus

Cited by 30 publications

References 36 publications

Stretch to See: Lateral Tension Strongly Determines Cell Survival in Long-Term Cultures of Adult Porcine Retina

Stretch to See: Lateral Tension Strongly Determines Cell Survival in Long-Term Cultures of Adult Porcine Retina

Measuring the Mechanical Properties of Living Cells Using Atomic Force Microscopy

Glia–neuron interactions in the mammalian retina

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