July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Impact of the ROCK inhibitor ripasudil on distribution of claudin-5 in vascular endothelial cells in diabetic retinopathy
Author Affiliations & Notes
  • Mitsuru Arima
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Shintaro Nakao
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Feng Hao
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
    China Medical University, Shenyang, China
  • Muneo Yamaguchi
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Kensuke Shibata
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Yoshihiro Kaizu
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Iori Wada
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Shigeo Yoshida
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Koh-hei Sonoda
    Ophthalmology, Kyushu University, Fukuoka, FUKUOKA, Japan
  • Footnotes
    Commercial Relationships   Mitsuru Arima, None; Shintaro Nakao, Kowa (P); Feng Hao, None; Muneo Yamaguchi, None; Kensuke Shibata, None; Yoshihiro Kaizu, None; Iori Wada, None; Shigeo Yoshida, None; Koh-hei Sonoda, Kowa (F)
  • Footnotes
    Support  MEXT KAKENHI Grant Number JP17K16997
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5356. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Mitsuru Arima, Shintaro Nakao, Feng Hao, Muneo Yamaguchi, Kensuke Shibata, Yoshihiro Kaizu, Iori Wada, Shigeo Yoshida, Koh-hei Sonoda; Impact of the ROCK inhibitor ripasudil on distribution of claudin-5 in vascular endothelial cells in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5356.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Diabetic macular edema (DME) is caused by vascular hyperpermeability associated with redistribution of claudin-5, a molecule that plays an essential role in tight junction assembly between retinal vascular endothelial cells. Here, we investigated the impact of a ROCK inhibitor, ripasudil, on claudin-5 expression and vascular barrier integrity in diabetic retinopathy by using in vitro and in vivo models.

Methods : In vitro, a brain microvascular endothelial cell line, bEND.3, was used to measure the claudin-5 expression and transendothelial electrical resistance (TEER) under conditions stimulated by the addition of either vascular endothelial growth factor (VEGF) or by vitreous fluid of DME, in the presence or absence of ripasudil. In vivo, Kimba mice, which show a transient overexpression of human VEGF in photoreceptor cells, were used to investigate the effect of ripasudil eye drops, intravitreal injection of bevacizumab (IVB), or the combination of both treatments on claudin-5 expression and on leakage of fluorescein dye from vascular vessels.

Results : In vitro, ROCK activity was increased in endothelial cells by addition of VEGF (p<0.05) as well as by addition of vitreous fluid of DME (p<0.05). Ripasudil did not affect VEGF- or DME vitreous fluid-induced reduction of claudin-5 expression in whole cell lysates. However, ripasudil maintained claudin-5 levels in the membrane fraction and the compound also inhibited a decrease in TEER under conditions stimulated by the addition of VEGF (p<0.01 and p<0.0001) or by addition of vitreous fluid of DME (p<0.05 and p<0.0001). In vivo, Kimba mice showed ROCK activation in the retina (p<0.01). Eye drops of ripasudil and IVB partially restored vascular barrier function, and the combination treatment inhibited the vascular hyperpermeability in an additive manner.

Conclusions : ROCK inhibition by ripasudil attenuated vascular hyperpermeability by maintaining claudin-5 in endothelial membranes. Ripasudil could be a new candidate drug for DME.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×