Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Reinhard, Jacqueline; Renner, Marina; Wiemann, Susanne; Shakoor, Daniel Atif; Stute, Gesa; Dick, H. Burkhard; Faissner, Andréas; Joachim, Stephanie C.

doi:10.1038/srep43470

Cited by 42 publications

(47 citation statements)

References 80 publications

(83 reference statements)

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“…Subsequently, an equal area for each staining was adjusted and cut out with the Corel Paint Shop Pro software (V13, Corel Corporation, Ottawa, ON, Canada). To measure the area as well as the intensity of PSD-95, gephyrin, VGluT1, NMDA receptor 1, and GABA-A receptor α3, the ImageJ software (National Institute of Health, Bethesda, MD, USA) was used [ 100 , 101 ] ( Figure A1 ). Raw image files were added to the ImageJ software ( Figure A1 A).…”

Section: Methodsmentioning

confidence: 99%

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Benning¹,

Reinehr²,

Grotegut³

et al. 2020

IJMS

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Glaucoma is identified by an irreversible retinal ganglion cell (RGC) loss and optic nerve damage. Over the past few years, the immune system gained importance in its genesis. In a glaucoma-like animal model with intraocular S100B injection, RGC death occurs at 14 days. In an experimental autoimmune glaucoma model with systemic S100B immunization, a loss of RGCs is accompanied by a decreased synaptic signal at 28 days. Here, we aimed to study synaptic alterations in these two models. In one group, rats received a systemic S100B immunization (n = 7/group), while in the other group, S100B was injected intraocularly (n = 6–7/group). Both groups were compared to appropriate controls and investigated after 14 days. While inhibitory post-synapses remained unchanged in both models, excitatory post-synapses degenerated in animals with intraocular S100B injection (p = 0.03). Excitatory pre-synapses tendentially increased in animals with systemic S100B immunization (p = 0.08) and significantly decreased in intraocular ones (p = 0.04). Significantly more n-methyl-d-aspartate (NMDA) receptors (both p ≤ 0.04) as well as gamma-aminobutyric acid (GABA) receptors (both p < 0.03) were observed in S100B animals in both models. We assume that an upregulation of these receptors causes the interacting synapse types to degenerate. Heightened levels of excitatory pre-synapses could be explained by remodeling followed by degeneration.

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Section: Methodsmentioning

confidence: 99%

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Benning¹,

Reinehr²,

Grotegut³

et al. 2020

IJMS

Self Cite

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“…Both retinae of each animal (five animals/group) were pooled for RNA preparation and cDNA synthesis as previously described. 18,21 The designed oligonucleotides for Quantitative real-time PCR (qRT-PCR) are shown in Table 3 18,21,23,24 P-values below 0.05 were considered statistically significant, *P < 0.05, **P < 0.01, ***P < 0.001.…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

Loss of retinal ganglion cells in a new genetic mouse model for primary open‐angle glaucoma

Reinehr

Koch

Weiß

et al. 2019

J Cellular Molecular Medi

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Primary open‐angle glaucoma (POAG) is one of the most common causes for blindness worldwide. Although an elevated intraocular pressure (IOP) is the main risk factor, the exact pathology remained indistinguishable. Therefore, it is necessary to have appropriate models to investigate these mechanisms. Here, we analysed a transgenic glaucoma mouse model (βB1‐CTGF) to elucidate new possible mechanisms of the disease. Therefore, IOP was measured in βB1‐CTGF and wildtype mice at 5, 10 and 15 weeks of age. At 5 and 10 weeks, the IOP in both groups were comparable ( P > 0.05). After 15 weeks, a significant elevated IOP was measured in βB1‐CTGF mice ( P < 0.001). At 15 weeks, electroretinogram measurements were performed and both the a‐ and b‐wave amplitudes were significantly decreased in βB1‐CTGF retinae (both P < 0.01). Significantly fewer Brn‐3a + retinal ganglion cells (RGCs) were observed in the βB1‐CTGF group on flatmounts ( P = 0.02), cross‐sections ( P < 0.001) and also via quantitative real‐time PCR ( P = 0.02). Additionally, significantly more cleaved caspase 3 + RGCs were seen in the βB1‐CTGF group ( P = 0.002). Furthermore, a decrease in recoverin + cells was observable in the βB1‐CTGF animals ( P = 0.004). Accordingly, a significant down‐regulation of Recoverin mRNA levels were noted ( P < 0.001). Gfap expression, on the other hand, was higher in βB1‐CTGF retinae ( P = 0.023). Additionally, more glutamine synthetase signal was noted ( P = 0.04). Although no alterations were observed regarding photoreceptors via immunohistology, a significant decrease of Rhodopsin ( P = 0.003) and Opsin mRNA ( P = 0.03) was noted. We therefore assume that the βB1‐CTGF mouse could serve as an excellent model for better understanding the pathomechanisms in POAG.

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“…Moreover, the aggravating effect of TNC on ischemic injury is also reported in other tissues. For instance, ischemia enhanced TNC expression in the optic nerve [16]. TNC deficient mice were more resistant to liver I/R injury [17].…”

Section: Discussionmentioning

confidence: 99%

Silencing of Tenascin-C inhibits hypoxia reoxygenation injury of cardiomyocyte through TLR4和NF-κB pathway

Zhang

et al. 2020

Preprint

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Background: Myocardial infarction (MI) is one of the leading causes of morbidity and mortality worldwide, and its main pathophysiological mechanism is myocardial ischemia/reperfusion (I/R) injury. TNC is an extracellular matrix glycoprotein, and high TNC expression was associated with MI and ventricular remodeling. The present study aimed to investigate the effect and the underlying mechanisms of TNC on myocardial I/R injury.Methods: Cardiomyocyte H9c2 cells was used to establish an in vitro hypoxia/reoxygenation (H/R) model, which were under hypoxia for 4 h and reoxygenation for 12 h. TNC was silenced by small interfering RNA (siRNA) in H9c2 cells.Results: TNC mRNA and protein expressions were increased by H/R. TNC knockdown by siRNA improved the cell viability in H/R-stimulated H9c2 cells. TNC knockdown reversed the H/R-induced increase in the apoptosis, as evidenced by reduced TUNEL+ cells and caspase-3 activity, and inhibited oxidative stress and inflammatory cytokine production. TNC silencing inhibits TLR4 mRNA and protein expressions and NF-kappa B signals, as evidenced by reduced nuclear NF-κB p65 and increased cytoplasmic I-κBα in H/R-stimulated H9c2 cells. All these cardioprotection against H/R by siTNC was reversed by TLR4 overexpression.Conclusions: TNC silencing prevents H/R-induced injury by inhibiting apoptosis and oxidative stress by inhibition of TLR4-NF-κB pathway.

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Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

Cited by 42 publications

References 80 publications

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Loss of retinal ganglion cells in a new genetic mouse model for primary open‐angle glaucoma

Silencing of Tenascin-C inhibits hypoxia reoxygenation injury of cardiomyocyte through TLR4和NF-κB pathway

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