July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Sublethal hyperthermia on retinal pigment epithelium - possible role of heat shock protein 70 and influence of the inhibition of vascular endothelial growth factor-mediated signaling
Author Affiliations & Notes
  • Yoko Miura
    Institute of Biomedical Optics, University of Luebeck, Luebeck, Germany
    Department of Ophhtalmology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
  • Katharina Kern
    Institute of Biomedical Optics, University of Luebeck, Luebeck, Germany
    Medical Laser Center Luebeck, Germany
  • Ralf Brinkmann
    Institute of Biomedical Optics, University of Luebeck, Luebeck, Germany
    Medical Laser Center Luebeck, Germany
  • Footnotes
    Commercial Relationships   Yoko Miura, None; Katharina Kern, None; Ralf Brinkmann, None
  • Footnotes
    Support  BMBF (Federal Ministry of Education and Research) (#13GW0043 C) and EOARD (European Office of Aerospace Research and Development) (# FA9550-15-1-0443)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3672. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Yoko Miura, Katharina Kern, Ralf Brinkmann; Sublethal hyperthermia on retinal pigment epithelium - possible role of heat shock protein 70 and influence of the inhibition of vascular endothelial growth factor-mediated signaling. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3672. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Vascular endothelial growth factor (VEGF)-A/VEGF-receptor (R)-2 signaling is essential for the development of pathological angiogenesis and for the pathogenesis of many retinal disorders. However, it is also important for the homeostasis of healthy blood vessels and is suggested to be an autocrine survival factor for retinal pigment epithelial (RPE) cells. In recent years, combination treatment of anti-VEGF with minimally invasive thermal laser irradiation is introduced as a new therapy option for retinal disorders. In this study, possible influence of VEGF-A/VEGFR2 inhibition on RPE cell responses to sublethal hyperthermia was investigated.

Methods : Confluent porcine RPE cell culture was heated over 10s by a thulium laser (wavelength: 1940 nm) to a maximal temperature of 43°C, which was previously confirmed as a sublethal heating. Some cultures were irradiated in the presence of anti-VEGFR2, which was added 2h before irradiation in the culture medium. At indicated time points (3h or 24h) after heating, cell viability was investigated with flow cytometry, extracellular VEGF-A with enzyme-linked immunosorbent assay (ELISA), and intracellular heat shock protein (Hsp) 70 with western blotting.

Results : While sublethal hyperthermia increased the number of vital RPE cells (117±9% of the non-irradiated cells) 24h after irradiation, this effect was significantly reduced under concomitant VEGFR2 inhibition (100±7%). Regarding the influence on intracellular Hsp70, the RPE cultures treated with VEGFR2 inhibitor contained significantly less amount of intracellular Hsp70 (63%) shortly (3h) after irradiation, whereas there was no more difference after 24h.

Conclusions : Results suggest that VEGF-A/VEGFR2 signaling pathway may be involved in RPE cell viability and in the activation of Hsp70 shortly after sublethal hyperthermia. Although further investigations are necessary, it is important to note, that the VEGF depletive condition may largely affect the RPE cell responses to sublethal retinal laser treatment. In other words, the timing between the injection of anti-VEGF agents and laser treatment might play a role in the treatment effect.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

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.

×