Induction of heat shock protein 70 in mouse RPE as an in vivo model of transpupillary thermal stimulation

Mooud Amirkavei, Marja Pitkänen, Ossi Kaikkonen, Kai Kaarniranta, Helder André, Ari Koskelainen*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)
24 Downloads (Pure)

Abstract

The induction of heat shock response in the macula has been proposed as a useful therapeutic strategy for retinal neurodegenerative diseases by promoting proteostasis and enhancing protective chaperone mechanisms. We applied transpupillary 1064 nm long-duration laser heating to the mouse (C57Bl/6J) fundus to examine the heat shock response in vivo. The intensity and spatial distribution of heat shock protein (HSP) 70 expression along with the concomitant probability for damage were measured 24 h after laser irradiation in the mouse retinal pigment epithelium (RPE) as a function of laser power. Our results show that the range of heating powers for producing heat shock response while avoiding damage in the mouse RPE is narrow. At powers of 64 and 70 mW, HSP70 immunostaining indicates 90 and 100% probability for clearly elevated HSP expression while the corresponding probability for damage is 20 and 33%, respectively. Tunel staining identified the apoptotic regions, and the estimated 50% damaging threshold probability for the heating (ED50) was ~72 mW. The staining with Bestrophin1 (BEST1) demonstrated RPE cell atrophy with the most intense powers. Consequently, fundus heating with a long-duration laser provides an approachable method to develop heat shock-based therapies for the RPE of retinal disease model mice.

Original languageEnglish
Article number2063
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume21
Issue number6
DOIs
Publication statusPublished - 2 Mar 2020
MoE publication typeA1 Journal article-refereed

Keywords

  • Age-related macular degeneration (AMD)
  • Heat shock protein 70 (HSP70)
  • Immunohistology
  • Mouse
  • Retinal pigment epithelium (RPE)
  • Transpupillary laser-induced heating

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