June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Necrotic Enlargement of Cone Photoreceptor Cells and the Release of High-mobility Group Box-1 in Retinitis Pigmentosa
Author Affiliations & Notes
  • Yusuke Murakami
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Yasuhiro Ikeda
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Shunji Nakatake
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Jun Funatsu
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Takashi Tachibana
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Kohta Fujiwara
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Shintaro Nakao
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Toshio Hisatomi
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Shigeo Yoshida
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Tatsuro Ishibashi
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Koh-hei Sonoda
    Department of Ophthalmology, Kyushu University, Fukuoka, Japan
  • Footnotes
    Commercial Relationships   Yusuke Murakami, None; Yasuhiro Ikeda, None; Shunji Nakatake, None; Jun Funatsu, None; Takashi Tachibana, None; Kohta Fujiwara, None; Shintaro Nakao, None; Toshio Hisatomi, None; Shigeo Yoshida, None; Tatsuro Ishibashi, None; Koh-hei Sonoda, None
  • Footnotes
    Support  KAKEN 16H06268
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3231. doi:
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    • Get Citation

      Yusuke Murakami, Yasuhiro Ikeda, Shunji Nakatake, Jun Funatsu, Takashi Tachibana, Kohta Fujiwara, Shintaro Nakao, Toshio Hisatomi, Shigeo Yoshida, Tatsuro Ishibashi, Koh-hei Sonoda; Necrotic Enlargement of Cone Photoreceptor Cells and the Release of High-mobility Group Box-1 in Retinitis Pigmentosa
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):3231.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : In retinitis pigmentosa (RP), rod cell death due to 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, in a mouse model of RP, cone cell death involves necrotic features and is partly mediated by receptor-interacting protein kinases. In the present study, we further investigate the possible involvement of necrotic cone photoreceptor cell death in RP.

Methods : The morphological changes of cone cells in a mouse model of RP (rd10 mice) were evaluated by immunostaining and transmission electron microscopy. In 10 RP patients and 7 control subjects, the cone mosaic images were obtained by adaptive optics scanning laser ophthalmoscopy (AO-SLO), and the cone cell diameters were measured using automated cone labeling program and scale selection method. The vitreous samples were collected from 10 RP patients and 10 controls, and the amounts of high-mobility group box-1 (HMGB1), which is released from necrotic cells, were measured by ELISA.

Results : In rd10 mice, dying cone cells exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, AO-SLO analysis revealed significantly increased percentages of enlarged cone cells to more than 6 μm in the RP patients (5.3 ± 2.5%) compared with the controls (0.6 ± 0.6%, P=0.0004). The vitreous of the RP patients contained significantly higher levels of HMGB1 compared with the controls (P=0.0312).

Conclusions : 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.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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