Stromal Cell-Derived Factor-1 Is Essential for Photoreceptor Cell Protection in Retinal Detachment

Otsuka, Hiroki; Arimura, Noboru; Sonoda, Shozo; Nakamura, Makoto; Hashiguchi, Teruto; Maruyama, Ikuro; Nakao, Shintaro; Hafezi-Moghadam, Ali; Sakamoto, Taiji

doi:10.2353/ajpath.2010.100134

Cited by 32 publications

(45 citation statements)

References 42 publications

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“…Undiluted vitreous samples (0.5-0.7 ml) were collected from approximately the same site during vitrectomy as described. 10,11 The vitreous was injected into sterile tubes, immediately placed on ice, centrifuged to remove cells and debris, and stored at À 80 1C until analyses. The clinical histories of all patients were obtained from their medical records.…”

Section: Human Vitreous Samplesmentioning

confidence: 99%

“…These parameters were determined as previously described. 11 Measurements of the vitreous levels of histone H3 and the levels of six inflammatory molecules (interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor (TNF)-a) were measured as previously described. 11 The concentration of histone H3 was determined in each vitreous sample by an enzyme-linked immunosorbent assay (ELISA).…”

Section: Human Vitreous Samplesmentioning

confidence: 99%

“…11 Measurements of the vitreous levels of histone H3 and the levels of six inflammatory molecules (interleukin (IL)-1b, IL-6, IL-8, IL-10, IL-12p70, and tumor necrosis factor (TNF)-a) were measured as previously described. 11 The concentration of histone H3 was determined in each vitreous sample by an enzyme-linked immunosorbent assay (ELISA). Briefly, polystyrene microtiter plates were coated with antihuman histone H3 polyclonal antibody, and the vitreous samples were added and incubated overnight at 2-8 1C.…”

Section: Human Vitreous Samplesmentioning

confidence: 99%

“…All concentrations that were below the detection limit were assigned a value of 0 in the statistical analyses as previously described. 11,[14][15][16] Animals and Induction of RD All experiments were performed in accordance with a statement describing the Use of Animals in Ophthalmic and Vision Research proposed by the Association for Research in Vision and Ophthalmology, and approval was obtained from our institutional Animal Care Committee. Brown Norway rats (Japan SLC, Shizuoka, Japan) were housed in covered cages and kept at a constant temperature and relative humidity with a regular 12:12-h light/dark schedule.…”

Section: Human Vitreous Samplesmentioning

confidence: 99%

“…This protein played a significant role in the pathological and healing processes as DAMP molecules. 10,11 The vitreous has different properties that helps maintain its transparency and its ability to protect the retina. However, its exact role and mechanisms of action have not been determined.…”

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confidence: 99%

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Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment

Kawano

Ito

Yamada³

et al. 2014

Laboratory Investigation

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Histones are DNA-binding proteins and are involved in chromatin remodeling and regulation of gene expression. Histones can be released after tissue injuries, and the extracellular histones cause cellular damage and organ dysfunction. Regardless of their clinical significance, the role and relevance of histones in ocular diseases are unknown. We studied the role of histones in eyes with retinal detachment (RD). Vitreous samples were collected during vitrectomy, and the concentration of histone H3 was measured by enzyme-linked immunosorbent assay. The location of the histones and related molecules was examined in a rat RD model. The release of histones and their effects on rat retinal progenitor cells R28 and ARPE-19 were evaluated in vitro. In addition, the protective role of the vitreous body against histones was tested. The intravitreal concentration of histones was higher in eyes with RD (mean, 30.9±9.8 ng/ml) than in control eyes (below the limit of detection, Po0.05). In the rat RD model, histone H3 was observed on the outer side of the detached retina and was associated with photoreceptor death. Histone H3 was released from cultured R28 by oxidative stress. Histones at a concentration 10 mg/ml induced the production of interleukin-8 in ARPE-19 cells (2.5-fold increase, Po0.05) that was mediated through the ERK1/2-and p38 MAPK-dependent pathways and Toll-like receptor 4. Histones were toxic to cells at concentrations of Z20 mg/ml. Vitreous body or hyaluronan decreased toxicity of histones by inhibiting diffusion of histones. These results indicate that histones are released from retinas with RD and may modulate the subretinal microenvironment by functioning as damage-associated molecular pattern molecules, thereby inducing proinflammatory cytokines or cell toxicity. In addition, the important role of the vitreous body and hyaluronan in protecting the retina from these toxic effects is suggested.

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Section: Human Vitreous Samplesmentioning

confidence: 99%

Section: Human Vitreous Samplesmentioning

confidence: 99%