Retinal Glial (Müller) Cells: Sensing and Responding to Tissue Stretch

Lindqvist, Niclas; Liu, Qing; Zajadacz, Joachim; Franze, Kristian; Reichenbach, Andreas

doi:10.1167/iovs.09-4159

Cited by 142 publications

(106 citation statements)

References 71 publications

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“…After partial detachment of the vitreous from the retina, vitreous fibers adhering to Müller cells at sites of vitreoretinal attachment exert tractional forces onto the cells; this activates the cells and results in cellular hypertrophy and proliferation as well as vascular leakage [85]. Mechanical stress induces calcium responses (likely induced by stretch-activated calcium-permeable cation channels [86]), activation of ERK1/2, and upregulation of the transcription factor c-Fos and of bFGF in Müller cells [87]. Mechanically stressed Müller cells release growth factors (e.g.…”

Section: Epiretinal Membrane Formationmentioning

confidence: 99%

“…Mechanically stressed Müller cells release growth factors (e.g. bFGF) and adenosine 5′-triphosphate (ATP) [87,88,89]. Calcium influx [through stretch-activated and voltage-gated calcium channels, and ionotropic purinergic (P2X 7 ) receptor channels] and subsequent activation of calcium-activated big-conductance potassium (BK) channels are required for growth factor- and ATP-induced proliferation of Müller cells [90,91,92,93,94].…”

Section: Epiretinal Membrane Formationmentioning

confidence: 99%

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Müller Glial Cells in Retinal Disease

Bringmann¹,

Wiedemann²

2011

Ophthalmologica

358

274

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Virtually all pathogenic stimuli activate Müller cells. Reactive Müller cells exert protective and toxic effects on photoreceptors and neurons. They contribute to oxidative stress and glutamate toxicity due to malfunctions of glutamate uptake and glutathione synthesis. Downregulation of potassium conductance disrupts transcellular potassium and water transport, resulting in neuronal hyperexcitability and edema. Protective effects of reactive Müller cells include upregulation of adenosine 5′-triphosphate (ATP)-degrading ectoenzymes, which enhances the extracellular availability of the neuroprotectant adenosine, abrogation of the osmotic release of ATP, which might protect retinal ganglion cells from apoptosis, and the release of antioxidants and neurotrophic factors. The dedifferentiation of reactive Müller cells to progenitor-like cells might have an impact on future therapeutic approaches. A better understanding of the gliotic mechanisms will be helpful in developing efficient therapeutic strategies aiming at increased protective and regenerative properties and decreased toxicity of reactive Müller cells.

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Section: Epiretinal Membrane Formationmentioning

confidence: 99%

Section: Epiretinal Membrane Formationmentioning

confidence: 99%

Müller Glial Cells in Retinal Disease

Bringmann¹,

Wiedemann²

2011

Ophthalmologica

358

274

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“…Two predominant approaches have been utilized to apply experimental forces to neurons. In the first approach, forces are applied to the entire neuron (Lu, Franze et al 2006;Chetta, Kye et al 2010;Lindqvist, Liu et al 2010). In the second approach, forces are applied directly to the axon by pulling on the growth cone.…”

Section: Overview Of the Axon Stretch Growth Bioreactor Systemmentioning

confidence: 99%

Axon Stretch Growth: The Mechanotransduction of Neuronal Growth

Loverde

Tolentino

Pfister

2011

JoVE

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During pre-synaptic embryonic development, neuronal processes traverse short distances to reach their targets via growth cone. Over time, neuronal somata are separated from their axon terminals due to skeletal growth of the enlarging organism (Weiss 1941;Gray, Hukkanen et al. 1992). This mechanotransduction induces a secondary mode of neuronal growth capable of accommodating continual elongation of the axon (Bray 1984;Heidemann and Buxbaum 1994;Heidemann, Lamoureux et al. 1995;Pfister, Iwata et al. 2004).Axon Stretch Growth (ASG) is conceivably a central factor in the maturation of short embryonic processes into the long nerves and white matter tracts characteristic of the adult nervous system. To study ASG in vitro, we engineered bioreactors to apply tension to the short axonal processes of neuronal cultures (Loverde, Ozoka et al. 2011). Here, we detail the methods we use to prepare bioreactors and conduct ASG. First, within each stretching lane of the bioreactor, neurons are plated upon a micro-manipulated towing substrate. Next, neurons regenerate their axonal processes, via growth cone extension, onto a stationary substrate. Finally, stretch growth is performed by towing the plated cell bodies away from the axon terminals adhered to the stationary substrate; recapitulating skeletal growth after growth cone extension.Previous work has shown that ASG of embryonic rat dorsal root ganglia neurons are capable of unprecedented growth rates up to 10mm/day, reaching lengths of up to 10cm; while concurrently resulting in increased axonal diameters (Smith, Wolf et al. 2001;Pfister, Iwata et al. 2004;Pfister, Bonislawski et al. 2006;Pfister, Iwata et al. 2006;Smith 2009). This is in dramatic contrast to regenerative growth cone extension (in absence of mechanical stimuli) where growth rates average 1mm/day with successful regeneration limited to lengths of less than 3cm (Fu and Gordon 1997;Pfister, Gordon et al. 2011). Accordingly, further study of ASG may help to reveal dysregulated growth mechanisms that limit regeneration in the absence of mechanical stimuli.

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“…It has also been suggested that these cells are able to regulate the biomechanical properties of the retina through changes in the expression of cytoskeletal intermediary filaments, such as GFAP and vimentin [28][29][30]. Müller cells have been found to express mechanosensory Ca 2+ ion channels [2,[31][32][33] which respond to changes in cell membrane tensility by Ca 2+ influx [31,35].…”

Section: The Role Of Müller Cellsmentioning

confidence: 99%

The Role of Mitochondria, Oxidative Stress, and the Radical-binding Protein A1M in Cultured Porcine Retina

Åkerström

Cederlund

Bergwik

et al. 2017

Current Eye Research

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Purpose: The purpose of this study was to explore the relationship between oxidative stress, antioxidant defense, mitochondrial structure and biomechanical tissue support in the isolated porcine retina. Methods:Full-thickness retinal sheets were isolated from adult porcine eyes. Retinas were cultured for 2 or 48 hours using 1) a previously established low-support explant protocol with photoreceptors positioned against the culture membrane (porous polycarbonate) or 2) a high-support procedure developed by our group, apposing the Müller cell endfeet and inner limiting membrane (ILM) against the membrane. The grafts were analyzed by quantitative PCR, immunohistochemistry, and transmission electron microscopy (TEM), and culture medium was assayed for the cell damage and oxidative stress markers lactate dehydrogenase and protein carbonyls. Results:In explants cultured with physical support to the inner border, cone photoreceptors were preserved and lactate dehydrogenase levels were reduced, although an initial (2h), transient, increased oxidative stress was observed. Elevated expression of the antioxidants A1M (α1-microglobulin) and heme oxygenase-1 were seen in the mitochondria-rich inner segments after 48h compared to low-support counterparts.Housekeeping gene expression suggested a higher degree of structural integrity of mitochondria in high-support explants, and TEM of inner segments confirmed preservation of a normal mitochondrial morphology. Conclusion:Providing retinal explants with inner retinal support leads to mobilization of antioxidant proteins, preservation of mitochondrial function and increased cell viability.Consequently, the failure of low-support retinal cultures to mobilize an adequate response to 2 the oxidative environment may play an key role in their rapid demise. These findings shed new light on pathological reactions in biomechanically related conditions in vivo.

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Retinal Glial (Müller) Cells: Sensing and Responding to Tissue Stretch

Abstract: A novel technique was developed for real-time monitoring of Müller cells during retinal stretch, which allowed the identification of Müller cells as a mechanoresponsive cell type. Mechanical stress triggers molecular responses in Müller cells that could prevent retinal damage.

Cited by 142 publications

References 71 publications

Müller Glial Cells in Retinal Disease

Müller Glial Cells in Retinal Disease

Axon Stretch Growth: The Mechanotransduction of Neuronal Growth

The Role of Mitochondria, Oxidative Stress, and the Radical-binding Protein A1M in Cultured Porcine Retina

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