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Hiroki Kawano, Takashi Ito, Ikuro Maruyama, Teruto Hashiguchi, Kazunori Miyata, Taiji Sakamoto; The use of hyaluronan in phacoemulsification protects human corneal endothelial cells from the noxious effect of extracellular histones.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2049.
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Histones, which are DNA binding proteins, are involved in chromatin remodeling and the regulation of gene expression. Histones can be released after tissue injuries or surgery, and extracellular histones including histone H3 are known to cause cellular damage and organ dysfunction as damage-associated molecular patterns (DAMPs). In spite of their clinical significance, the role and relevance of extracellular histones in ocular diseases are unknown. We had described that extracellular histones from the detached retina can affect the subretinal microenvironment by functioning as DAMPs, thereby inducing pro-inflammatory cytokines or cell toxicity. Furthermore, we had shown the role of the vitreous body and specifically hyaluronan in protecting the retina from the histone induced noxious effects. The purpose of this study is to investigate the possible role of extracellular histones from human corneal endothelial cells (HCEC) in phacoemulsification.
Cultured primary HCEC were exposed to histones and the secretion of interleukin 6 (IL-6) was evaluated by enzyme-linked immunosorbent assay. The effect of specific inhibitors of ERK, JNK, and p38 MAPK were evaluated. The protective effect of hyaluronan on this phenomenon was also studied. The presence of histone after phacoemulsification in a swine eye was examined immunohistochemistry.
The secretion of IL-6 was significantly increased with histones in a dose dependent manner (P < 0.01). Histone-induced IL-6 production was significantly decreased with ERK1/2 and p-38 MAPK inhibitors (P < 0.01). Hyaluronan decreased IL-6 secretions from HCEC stimulated by histones (P < 0.01). Histones were present in the anterior chamber of swine eyes which received phacoemulsification.
Extracellular histones are released after phacoemulsification, which can stimulate the secretion of proinflammatory cytokine IL-6 by HCEC. Intraoperative use of hyaluronan may decrease the harmful effect of extracellular histones from damaged tissues.
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