July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Overexpressing HSF1 prevents retinal neuronal injury in ischemic retinopathy
Author Affiliations & Notes
  • FAN XIA
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
    Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  • Wei Liu
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
    Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  • Yonju Ha
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
  • Shuang Zhu
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
  • Yi Li
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
    Eye Hospital, Tianjin Medical University, China
  • Oluwarotimi Folorunso
    Department of Pharmacology and Toxicology, University of Texas Medical Branch, Texas, United States
  • Aryan Pashaei-Marandi
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
  • Pei Yi LIN
    Thermo Fisher Scientific, New York, United States
  • Ronald G Tilton
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
    Internal Medicine, University of Texas Medical Branch, Texas, United States
  • Anson P Pierce
    Thermo Fisher Scientific, New York, United States
  • Hua Liu
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
  • Wenbo Zhang
    Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, GALVESTON, Texas, United States
  • Footnotes
    Commercial Relationships   FAN XIA, None; Wei Liu, None; Yonju Ha, None; Shuang Zhu, None; Yi Li, None; Oluwarotimi Folorunso, None; Aryan Pashaei-Marandi, None; Pei Yi LIN, None; Ronald G Tilton, None; Anson P Pierce, None; Hua Liu, None; Wenbo Zhang, None
  • Footnotes
    Support  NIH grants EY022694, EY026629 and AG055771, and Retina Research Foundation (to W.Z.); and American Heart Association 17SDG33630151 (to H.L.)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1633. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      FAN XIA, Wei Liu, Yonju Ha, Shuang Zhu, Yi Li, Oluwarotimi Folorunso, Aryan Pashaei-Marandi, Pei Yi LIN, Ronald G Tilton, Anson P Pierce, Hua Liu, Wenbo Zhang; Overexpressing HSF1 prevents retinal neuronal injury in ischemic retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1633. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Heat shock transcription factor 1 (HSF1), a stress-responsive protein, has been shown to be important in response to cellular stress stimuli, including ischemia. However, its specific role in ischemic retinopathy remains unknown. In this study, we studied the role of HSF1 in retinal neuronal damage after ischemic injury in vivo.

Methods : Studies were performed on wild-type (WT) mice and HSF1 transgenic mice carrying full-length human HSF1 gene. Retinal ischemia-reperfusion (IR) was induced by inserting an infusion needle into the anterior chamber of the right eye and elevating a saline reservoir connected to the needle to raise the intraocular pressure to 110 mm Hg for 45 minutes. HSF1, HSP70, molecules in the ER stress branches, tau phosphorylation, inflammatory molecules and retinal ganglion cell (RGC) injury were determined by immunohistochemistry, Western blot or quantitative PCR. Dark-adapted electroretinography (ERG) analysis was performed to determine the function of RGCs after IR.

Results : HSF1 was primarily localized in retinal ganglion cell and inner nuclear layers. Its mRNA and protein expressions were significantly increased in the retina at 6 hours and 12 hours after IR injury (mRNA: 182.6 ± 20.7 % & 146.6 ± 18.6%; protein: 301.5 ± 40.5 % & 221.2 ± 48.2 % of non-injured retina, n=4, p<0.05), followed by a return to normal level at 24 hours after injury. Overexpression of HSF1 significantly induced chaperone protein Hsp70, alleviated endoplasmic-reticulum (ER) stress, leading to decreased tau aggregation and attenuated inflammatory response at 12 hours after IR injury. Furthermore, at 12 hours after IR, TUNEL and PI uptake assays demonstrated that retinal neuronal apoptosis and necroptosis were significantly abrogated by 79.6 % (n=4, p<0.05) and 63.6 % (n=6, p<0.05) in HSF1 transgenic mice. As a result, loss of RGCs was dramatically decreased by 46.4 % (n=6-7, p<0.05), and their function was preserved in HSF1 transgenic mice.

Conclusions : HSF1 is neuroprotective against retinal IR injury and boosting HSF1 expression could be a beneficial strategy to limit neuronal degeneration in retinal diseases.

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.

×