Reversible reactivity by optic nerve astrocytes

Sun, Daniel; Qu, Juan; Jakobs, Tatjana C.

doi:10.1002/glia.22507

Cited by 87 publications

(85 citation statements)

References 59 publications

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“…These morphological properties are quite similar to the morphology of optic nerve head astrocytes in vivo that was observed from transverse sections of the optic nerve head of B6.hGFAPpr-EGFP mice, in which astrocytes express EGFP (Fig. 1C), as well as that was described in previous studies (Sun et al, 2009, 2010; Sun et al, 2013). For comparison, a microglial cell from a B6.129P-Cx3cr1 tm1Litt /J mouse was imaged in the same way (Fig.…”

Section: Detailed Methodssupporting

confidence: 87%

“…These two genes were chosen to validate the method because the changes in gene expression for both were known from prior experiments. GFAP is significantly (though not dramatically) up-regulated on the protein level after optic nerve crush (Sun et al, 2013). Both GFAP and vimentin are not significantly differentially regulated in whole optic nerve head tissue after injury when assayed by microarray (Qu and Jakobs, 2013), and are up-regulated slightly (~1.25-fold) when assayed by qPCR.…”

Section: Detailed Methodsmentioning

confidence: 99%

“…The transgenic hGFAPpr-EGFP mice on the FVB/N background (Nolte et al, 2001) were obtained from the laboratory of Helmut Kettenmann (Max Delbruck Center, Berlin, Germany). This mouse strain displays bright expression of enhanced green fluorescent protein (EGFP) in many, but not all astrocytes, thus the complete morphology of individual astrocytes can be observed directly (Sun et al, 2009, 2010; Sun et al, 2013). We crossed the hGFAPpr-EGFP mice with C57BL/6 mice for at least six generations to remove the retinal degeneration mutation in the FVB/N-derived transgenic mice.…”

Section: Materials and Suppliesmentioning

confidence: 99%

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Isolation of intact astrocytes from the optic nerve head of adult mice

Choi

Sun

Jakobs

2015

Experimental Eye Research

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The astrocytes of the optic nerve head are a specialized subtype of white matter astrocytes that form the direct cellular environment of the unmyelinated ganglion cell axons. Due to their potential involvement in glaucoma, these astrocytes have become a target of research. Due to the heterogeneity of the optic nerve tissue, which also contains other cell types, in some cases it may be desirable to conduct gene expression studies on small numbers of well-characterized astrocytes or even individual cells. Here, we describe a simple method to isolate individual astrocytes. This method permits obtaining astrocytes with intact morphology from the adult mouse optic nerve and reduces contamination of the isolated astrocytes by other cell types. Individual astrocytes can be recognized by their morphology and collected under microscopic control. The whole procedure can be completed in 2-3 hours. We also discuss downstream applications like multiplex single-cell PCR and quantitative PCR (qPCR).

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Section: Detailed Methodssupporting

confidence: 87%

Section: Detailed Methodsmentioning

confidence: 99%

Section: Materials and Suppliesmentioning

confidence: 99%

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Isolation of intact astrocytes from the optic nerve head of adult mice

Choi

Sun

Jakobs

2015

Experimental Eye Research

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“…Astrocytes are positioned along the connective tissues of the ONH, including the laminar beams in the primate ONH [10]. Astrocytes exhibit multiple extensions that enter and unsheathe axon bundles [7, 11, 12]. These astrocyte extensions further couple the meningeal vasculature to axons [13, 14], and are involved in neural development and synapse formation [15], metabolic and ionic support of ONH axons [16–18], facilitate mitochondrial transcellular degradation from retinal ganglion cell axons [19], and phagocytosis of myelin segments within the optic nerve [20, 21].…”

Section: Introductionmentioning

confidence: 99%

Astrocyte Structural and Molecular Response to Elevated Intraocular Pressure Occurs Rapidly and Precedes Axonal Tubulin Rearrangement within the Optic Nerve Head in a Rat Model

et al. 2016

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Glaucomatous axon injury occurs at the level of the optic nerve head (ONH) in response to uncontrolled intraocular pressure (IOP). The temporal response of ONH astrocytes (glial cells responsible for axonal support) to elevated IOP remains unknown. Here, we evaluate the response of actin-based astrocyte extensions and integrin-based signaling within the ONH to 8 hours of IOP elevation in a rat model. IOP elevation of 60 mm Hg was achieved under isoflurane anesthesia using anterior chamber cannulation connected to a saline reservoir. ONH astrocytic extension orientation was significantly and regionally rearranged immediately after IOP elevation (inferior ONH, 43.2° ± 13.3° with respect to the anterior-posterior axis versus 84.1° ± 1.3° in controls, p<0.05), and re-orientated back to baseline orientation 1 day post IOP normalization. ONH axonal microtubule filament label intensity was significantly reduced 1 and 3 days post IOP normalization, and returned to control levels on day 5. Phosphorylated focal adhesion kinase (FAK) levels steadily decreased after IOP normalization, while levels of phosphorylated paxillin (a downstream target of FAK involved in focal adhesion dynamics) were significantly elevated 5 days post IOP normalization. The levels of phosphorylated cortactin (a downstream target of Src kinase involved in actin polymerization) were significantly elevated 1 and 3 days post IOP normalization and returned to control levels by day 5. No significant axon degeneration was noted by morphologic assessment up to 5 days post IOP normalization. Actin-based astrocyte structure and signaling within the ONH are significantly altered within hours after IOP elevation and prior to axonal cytoskeletal rearrangement, producing some responses that recover rapidly and others that persist for days despite IOP normalization.

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“…Several laboratories have also used short-term elevations in IOP, from 30 min to several hours, as a unique approach to determine ONH and retinal responses to IOP (Abbott et al, 2014; Balaratnasingam et al, 2007, 2008; Sun et al, 2013). Others have combined experimental glaucoma with electroretinography (ERG) as a non-invasive test to measure the impact of short term IOP exposures on the ONH and retina, and have used this system to determine the effects of age, dietary restriction and mitochondrial abnormalities on their response (Kong et al, 2011, 2012).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of elevated intraocular pressure and reduced ocular perfusion pressure on retinal capillary bed filling and total retinal blood flow in rats by OMAG/OCT

Zhi

Cepurna

Johnson

et al. 2015

Microvascular Research

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Purpose To determine if retinal capillary filling is preserved in the face of acutely elevated intraocular pressure (IOP) in anesthetized rats, despite a reduction in total retinal blood flow (RBF), using optical microangiography/optical coherence tomography (OMAG/OCT). Methods OMAG provided the capability of depth-resolved imaging of the retinal microvasculature down to the capillary level. Doppler OCT was applied to measure the total RBF using an enface integration approach. The microvascular pattern, capillary density, and total RBF were monitored in vivo as the IOP was increased from 10 to 100 mm Hg in 10 mm Hg intervals and returned back to 10 mm Hg. Results In animals with mean arterial pressure (MAP) of 102 ± 4 mm Hg (n = 10), when IOP was increased from 0 to 100 mm Hg, the capillary density remained at or above 80% of baseline for the IOP up to 60 mm Hg [or ocular perfusion pressure (OPP) at 40 mm Hg]. This was then decreased, achieving 60% of baseline at IOP 70 mm Hg and OPP of 30 mm Hg. Total RBF was unaffected by moderate increases in IOP up to 30 mm Hg, beyond which total RBF decreased linearly, reaching 50% of baseline at IOP 60 mm Hg and OPP 40 mm Hg. Both capillary density and total RBF were totally extinguished at 100 mm Hg, but fully recovered when IOP returned to baseline. By comparison, a separate group of animals with lower MAP (mean = 75 ± 6 mm Hg, n = 7) demonstrated comparable decreases in both capillary filling and total RBF at IOPs that were 20 mm Hg lower than in the initial group. Both were totally extinguished at 80 mm Hg, but fully recovered when IOP returned to baseline. Relationships of both parameters to OPP were unchanged. Conclusion Retinal capillary filling and total RBF responses to IOP elevation can be monitored non-invasively by OMAG/OCT and both are influenced by OPP. Retinal capillary filling was relatively preserved down to a perfusion pressure of 40 mm Hg, despite a linear reduction in total RBF.

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Reversible reactivity by optic nerve astrocytes

Cited by 87 publications

References 59 publications

Isolation of intact astrocytes from the optic nerve head of adult mice

Isolation of intact astrocytes from the optic nerve head of adult mice

Astrocyte Structural and Molecular Response to Elevated Intraocular Pressure Occurs Rapidly and Precedes Axonal Tubulin Rearrangement within the Optic Nerve Head in a Rat Model

Evaluation of the effect of elevated intraocular pressure and reduced ocular perfusion pressure on retinal capillary bed filling and total retinal blood flow in rats by OMAG/OCT

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