Photoreceptor apoptosis in human retinal detachment

Arroyo, Jorge G.; Yang, Liu; Bula, Deisy V.; Chen, Dong Feng

doi:10.1016/j.ajo.2004.11.046

Cited by 193 publications

(148 citation statements)

References 14 publications

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“…[4][5][6][7] Meanwhile, we also noticed the increased expression of GADD153 protein, which peaked at 0.5, 1, 2, and 4 d after RD. Spatially, the GADD153-positive cells were only found in ONL, in which most of apoptotic cells presented.…”

Section: Discussionmentioning

confidence: 87%

“…[1][2][3] Photoreceptor apoptosis was held responsible for neuroretinal cell loss in both animal RD models and in clinical research. [4][5][6][7] Traditionally, cell apoptosis has two major pathways: the death receptor-mediated pathway and mitochondrion-mediated pathway. Earlier studies mainly focused on the mitochondrion-mediated pathway; the existence of mitochondrion-mediated pathway has been confirmed in the apoptosis of photoreceptors whereby the inhibition of key factors in above pathway prevented the photoreceptors from apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

Liu

Qian

Wang

et al. 2009

Eye

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Purpose To investigate the expression of endoplasmic reticulum (ER) stress-related genes, glucose-regulated protein 78 (GRP78) and growth arrest DNA damage-inducible gene 153 (GADD153)/CPEBP homologous protein (CHOP), in rat retinal detachment (RD) model. Materials and methods At various time points after RD, the apoptosis of retinal cells was detected by TdT-mediated fluorescein-16-dUTP nick-end labelling (TUNEL) assay; GRP78 and GADD153 mRNA levels were detected by reverse transcription (RT)-PCR; proteins were detected by western blotting analysis; protein distributions in the retinal cells were observed by immunofluorescence using laser-scanning confocal microscope. Results After RD, the apoptosis was peaked on 2-4 d and then dropped down. The GRP78 mRNA and GADD153 mRNA levels in RD groups on 0.5, 1, 2, and 4 d were all significantly higher than those in the control group (Po0.05). The expression of GRP78 mRNA peaked on 1-2 d after RD. Expression of GRP78 protein was significantly higher than that in the normal control group on 0.5, 1, 2, 4, 8, 16, and 32 d after RD (Po0.05). The expression of GRP78 protein was observed in all the layers of retina in the RD groups, and peaked on 8, 16, and 32 d. The expression of GADD153 protein, mostly in photoreceptor layers, was significantly higher than that in the control group on 0.5, 1, 2, and 4 d after RD (Po0.05). Conclusions ER stress-related markers, GRP78 and GADD153, are elevated after RD.The elevation of GADD153 is in parallel with the post-RD apoptosis of retinal cells, suggesting that ER stress-mediated death is likely to be activated after RD and involved in post-RD vision loss.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

Liu

Qian

Wang

et al. 2009

Eye

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“…During studies on RD, photoreceptor degeneration after RD had been thought to be mainly caused by apoptosis. 15,16 Hisatomi et al 32 demonstrated the presence of apoptotic debris in the subretinal space of rat RD. In the present study, considering our immunohistochemistry results from the same rat model of RD, so-called necrotic debris, which is HMGB1 positive and TUNEL negative, was found to be present.…”

Section: Discussionmentioning

confidence: 99%

“…Photoreceptor degeneration due to RD is thought to be executed by apoptosis 15,16 and necrosis, 17 which usually occur after tissue damage. Although retinal cell death and the following reactive responses must occur in almost all forms of retinal disease including RD, 18 data regarding the relationship among cell death, danger, and responses in the eye, have been very limited, especially in terms of danger signals.…”

mentioning

confidence: 99%

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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“…Physical separation of photoreceptors is seen in various retinal disorders, including age-related macular degeneration (1), diabetic retinopathy (2), as well as rhegmatogenous (i.e., caused by a break in the retina) retinal detachment (3,4). Although surgery is carried out to reattach the retina, only two fifths of patients with rhegmatogenous retinal detachment involving the macula, a region essential for central vision, recover 20/40 or better vision because of photoreceptor death (4,5). Thus, identification of the mechanisms that underlie photoreceptor death is critical to developing new treatment strategies for these diseases.…”

mentioning

confidence: 99%

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis

Trichonas

Murakami

Thanos

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

279

276

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Apoptosis has been shown to be a significant form of cell loss in many diseases. Detachment of photoreceptors from the retinal pigment epithelium, as seen in various retinal disorders, causes photoreceptor loss and subsequent vision decline. Although caspasedependent apoptotic pathways are activated after retinal detachment, caspase inhibition by the pan-caspase inhibitor Z-VAD fails to prevent photoreceptor death; thus, we investigated other pathways leading to cell loss. Here, we show that receptor interacting protein (RIP) kinase-mediated necrosis is a significant mode of photoreceptor cell loss in an experimental model of retinal detachment and when caspases are inhibited, RIP-mediated necrosis becomes the predominant form of death. RIP3 expression, a key activator of RIP1 kinase, increased more than 10-fold after retinal detachment. Morphological assessment of detached retinas treated with Z-VAD showed decreased apoptosis but significantly increased necrotic photoreceptor death. RIP1 kinase inhibitor necrostatin-1 or Rip3 deficiency substantially prevented those necrotic changes and reduced oxidative stress and mitochondrial release of apoptosis-inducing factor. Thus, RIP kinase-mediated programmed necrosis is a redundant mechanism of photoreceptor death in addition to apoptosis, and simultaneous inhibition of RIP kinases and caspases is essential for effective neuroprotection and may be a novel therapeutic strategy for treatment of retinal disorders.degenerations | necroptosis P hotoreceptor death and subsequent visual decline occurs when the photoreceptors are separated from the underlying retinal pigment epithelium. Physical separation of photoreceptors is seen in various retinal disorders, including age-related macular degeneration (1), diabetic retinopathy (2), as well as rhegmatogenous (i.e., caused by a break in the retina) retinal detachment (3, 4). Although surgery is carried out to reattach the retina, only two fifths of patients with rhegmatogenous retinal detachment involving the macula, a region essential for central vision, recover 20/40 or better vision because of photoreceptor death (4, 5). Thus, identification of the mechanisms that underlie photoreceptor death is critical to developing new treatment strategies for these diseases.Apoptosis and necrosis are two major cell death modalities (6). Apoptosis is a highly regulated process involving the caspase family of cysteine proteases. In contrast, necrosis has been considered a passive, unregulated form of cell death; however, recent evidence indicates that some necrosis can be induced by regulated signal transduction pathways such as those mediated by receptor interacting protein (RIP) kinases, especially in conditions in which caspases are inhibited or cannot be activated efficiently (7,8). Stimulation of the Fas and TNFR family of death domain receptors is known to mediate apoptosis in most cell types through the activation of the extrinsic caspase pathway. In addition, in certain cells deficient for caspase-8 or treated with the pan-caspa...

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Photoreceptor apoptosis in human retinal detachment

Cited by 193 publications

References 14 publications

Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

Expression of two endoplasmic reticulum stress markers, GRP78 and GADD153, in rat retinal detachment model and its implication

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

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis

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