Neuroprotective effects of HSF1 in retinal ischemia-reperfusion injury

Wei Liu, Fan Xia, Yonju Ha, Shuang Zhu, Yi Li, Oluwarotimi Folorunso, Aryan Pashaei-Marandi, Pei Yi Lin, Ronald G. Tilton, Anson P. Pierce, Hua Liu, Wenbo Zhang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

PURPOSE. Retinal ischemia, a common cause of several vision-threatening diseases, contributes to the death of retinal neurons, particularly retinal ganglion cells (RGCs). Heat shock transcription factor 1 (HSF1), a stress-responsive protein, has been shown to be important in response to cellular stress stimuli, including ischemia. This study is to investigate whether HSF1 has a role in retinal neuronal injury in a mouse model of retinal ischemia-reperfusion (IR). METHODS. 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 endoplasmic reticulum (ER) stress branches, tau phosphorylation, inflammatory molecules, and RGC injury were determined by immunohistochemistry, Western blot, or quantitative PCR. RESULTS. HSF1 expression was significantly increased in the retina 6 hours after IR. Using our novel transgenic mice carrying full-length human HSF gene, we demonstrated that IR-induced retinal neuronal apoptosis and necroptosis were abrogated 12 hours after IR. RGCs and their function were preserved in the HSF1 transgenic mice 7 days after IR. Mechanistically, the beneficial effects of HSF1 may be mediated by its induction of chaperone protein Hsp70 and alleviation of ER stress, leading to decreased tau phosphorylation and attenuated inflammatory response 12 to 24 hours after IR. CONCLUSIONS. These data provide compelling evidence that HSF1 is neuroprotective against retinal IR injury, and boosting HSF1 expression may be a beneficial strategy to limit neuronal degeneration in retinal diseases.

Original languageEnglish (US)
Pages (from-to)965-977
Number of pages13
JournalInvestigative Ophthalmology and Visual Science
Volume60
Issue number4
DOIs
StatePublished - Mar 2019

Keywords

  • ER stress
  • HSF1
  • Heat shock protein
  • Neuronal injury
  • Retinal ischemia

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Liu, W., Xia, F., Ha, Y., Zhu, S., Li, Y., Folorunso, O., Pashaei-Marandi, A., Lin, P. Y., Tilton, R. G., Pierce, A. P., Liu, H., & Zhang, W. (2019). Neuroprotective effects of HSF1 in retinal ischemia-reperfusion injury. Investigative Ophthalmology and Visual Science, 60(4), 965-977. https://doi.org/10.1167/iovs.18-26216