Early Activation of Inflammation- and Immune Response-Related Genes after Experimental Detachment of the Porcine Retina

Hollborn, Margrit; Francke, Mike; Iandiev, Ianors; Bühner, Eva; Foja, C.; Kohen, Leon; Reichenbach, Andreas; Wiedemann, Peter; Bringmann, Andreas; Uhlmann, Susann

doi:10.1167/iovs.07-0879

Cited by 59 publications

(49 citation statements)

References 42 publications

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“…Interestingly, HMGB1 appeared to be robustly upregulated in both the photoreceptors and the other retinal cells at day 3 after RD inductions, and DAPI staining was inversely downregulated at the same time ( Figure 2b, e and h). As previous reports demonstrated that dramatic alterations of retinal gene expression occurred after RD, 31 this high level of HMGB1 expression might be related to the active gene transcription. HMGB1 in the nucleus might be stress responsive and necessary for proper transcription after RD tissue damage.…”

Section: Hmgb1 Is Present In Cultured Retinal Cell and Released Extramentioning

confidence: 68%

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

Arimura

Kii

Hashiguchi

et al. 2009

Laboratory Investigation

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High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signalregulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

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Section: Hmgb1 Is Present In Cultured Retinal Cell and Released Extramentioning

confidence: 68%

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

Arimura

Kii

Hashiguchi

et al. 2009

Laboratory Investigation

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“…48 In addition, NFB induces the expression of genes involved in chronic and acute inflammatory responses, 49 which concurred with the association of both HtrA1 and VEGF with inflammation. 38,50 Further studies should be conducted to validate this hypothesis. Unlike the previous studies, 16,17 we found no association between vitreous HtrA1 levels and rs11200638 genotypes (Table 4).…”

Section: Discussionmentioning

confidence: 95%

“…2) might be related to inflammatory and stress responses. [37][38][39] HtrA1 is associated with geographic atrophy 29 and drusen, 30,31 and is upregulated in response to estrogeninduced oxidative stress. 40 We also found that human fetal RPE cells responded to chemical-induced stress by simultaneous upregulations of HTRA1 and VEGFA after treatments with tunicamycin and DTT (Figs.…”

Section: Discussionmentioning

confidence: 99%

Interactive Expressions of HtrA1 and VEGF in Human Vitreous Humors and Fetal RPE Cells

Yam

Chen

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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“…After retinal injury, such as retinal detachment, Müller cells upregulate inflammatory factors, including monocyte chemoattractant protein-1, which recruit phagocytotic monocytes/macrophages and microglial cells to the injured area [40,41]. Invading macrophages and neutrophils release oxygen free radicals and cytotoxic cytokines, which play critical roles in photoreceptor apoptosis after retinal detachment [42] and in neuronal degeneration after ischemia-reperfusion [43].…”

Section: Müller Cell Gliosismentioning

confidence: 99%

“…Likewise, argon laser photocoagulation slows photoreceptor degeneration by induction of bFGF in Müller cells [52]. Other neuroprotective effects of gliosis include the production and release of antioxidants, such as glutathione (see below), pyruvate, α-ketoglutarate, metallothionein, lysozyme, ceruloplasmin, heme oxygenase and reduced ascorbate [41,53,54,55,56,57,58]. Müller cells phagocytize cellular debris [59] and blood-derived proteins (fig.…”

Section: Müller Cell Gliosismentioning

confidence: 99%

Müller Glial Cells in Retinal Disease

Bringmann¹,

Wiedemann²

2011

Ophthalmologica

Self Cite

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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Early Activation of Inflammation- and Immune Response-Related Genes after Experimental Detachment of the Porcine Retina

Cited by 59 publications

References 42 publications

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

Interactive Expressions of HtrA1 and VEGF in Human Vitreous Humors and Fetal RPE Cells

Müller Glial Cells in Retinal Disease

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