Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa

Y. Murakami, Y. Ikeda, S. Nakatake, T. Tachibana, K. Fujiwara, N. Yoshida, S. Notomi, S. Nakao, T. Hisatomi, J. W. Miller, Dg Vavvas, Kh Sonoda, T. Ishibashi

研究成果: ジャーナルへの寄稿学術誌査読

14 被引用数 (Scopus)

抄録

Retinitis pigmentosa (RP) refers to a group of inherited retinal degenerations resulting form rod and cone photoreceptor cell death. The rod cell death due to deleterious genetic mutations has been shown to occur mainly through apoptosis, whereas the mechanisms and features of the secondary cone cell death have not been fully elucidated. Our previous study showed that the cone cell death in rd10 mice, an animal model of RP, involves necrotic features and is partly mediated by the receptor interacting protein kinase. However, the relevancy of necrotic cone cell death in human RP patients remains unknown. In the present study, we showed that dying cone cells in rd10 mice exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, live imaging of cone cells by adaptive optics scanning laser ophthalmoscopy revealed significantly increased percentages of enlarged cone cells in the RP patients compared with the control subjects. The vitreous of the RP patients contained significantly higher levels of high-mobility group box-1, which is released extracellularly associated with necrotic cell death. These findings suggest that necrotic enlargement of cone cells is involved in the process of cone degeneration, and that necrosis may be a novel target to prevent or delay the loss of cone-mediated central vision in RP.

本文言語英語
論文番号15058
ジャーナルCell Death Discovery
1
1
DOI
出版ステータス出版済み - 12月 21 2015

!!!All Science Journal Classification (ASJC) codes

  • 免疫学
  • 細胞および分子神経科学
  • 細胞生物学
  • 癌研究

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