Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response

Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response

Heat shock protein 27 (HSP27) is one of the small molecular chaperones and is involved in many cell mechanisms. Besides the known protective and helpful functions of intracellular HSP27, very little is known about the mode of action of extracellular HSP27. In a previous study, we showed that intravi...

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Main Authors: Pia Grotegut, Philipp Johannes Hoerdemann, Sabrina Reinehr, Nupur Gupta, H. Burkhard Dick, Stephanie C. Joachim
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
Subjects:
glaucoma
heat shock protein 27 (HSP27)
retinal ganglion cell degeneration
apoptosis
T-cells
microglia
Online Access:https://www.mdpi.com/1422-0067/22/2/513
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spelling doaj-3db10609724a4c82bb9f5c6a3ec810572021-01-07T00:06:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-012251351310.3390/ijms22020513Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell ResponsePia Grotegut0Philipp Johannes Hoerdemann1Sabrina Reinehr2Nupur Gupta3H. Burkhard Dick4Stephanie C. Joachim5Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, GermanyExperimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, GermanyHeat shock protein 27 (HSP27) is one of the small molecular chaperones and is involved in many cell mechanisms. Besides the known protective and helpful functions of intracellular HSP27, very little is known about the mode of action of extracellular HSP27. In a previous study, we showed that intravitreal injection of HSP27 led to neuronal damage in the retina and optic nerve after 21 days. However, it was not clear which degenerative signaling pathways were induced by the injection. For this reason, the pathological mechanisms of intravitreal HSP27 injection after 14 days were investigated. Histological and RT-qPCR analyses revealed an increase in endogenous HSP27 in the retina and an activation of components of the intrinsic and extrinsic apoptosis pathway. In addition, an increase in nucleus factor-kappa-light-chain-enhancer of activated B cells (NFκB), as well as of microglia/macrophages and T-cells could be observed. In the optic nerve, however, only an increased apoptosis rate was detectable. Therefore, the activation of caspases and the induction of an incipient immune response seem to be the main triggers for retinal degeneration in this intravitreal HSP27 model.https://www.mdpi.com/1422-0067/22/2/513glaucomaheat shock protein 27 (HSP27)retinal ganglion cell degenerationapoptosisT-cellsmicroglia
collection DOAJ
language English
format Article
sources DOAJ
author Pia Grotegut
Philipp Johannes Hoerdemann
Sabrina Reinehr
Nupur Gupta
H. Burkhard Dick
Stephanie C. Joachim
spellingShingle Pia Grotegut
Philipp Johannes Hoerdemann
Sabrina Reinehr
Nupur Gupta
H. Burkhard Dick
Stephanie C. Joachim
Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response
International Journal of Molecular Sciences
glaucoma
heat shock protein 27 (HSP27)
retinal ganglion cell degeneration
apoptosis
T-cells
microglia
author_facet Pia Grotegut
Philipp Johannes Hoerdemann
Sabrina Reinehr
Nupur Gupta
H. Burkhard Dick
Stephanie C. Joachim
author_sort Pia Grotegut
title Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response
title_short Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response
title_full Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response
title_fullStr Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response
title_full_unstemmed Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-cell Response
title_sort heat shock protein 27 injection leads to caspase activation in the visual pathway and retinal t-cell response
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2021-01-01
description Heat shock protein 27 (HSP27) is one of the small molecular chaperones and is involved in many cell mechanisms. Besides the known protective and helpful functions of intracellular HSP27, very little is known about the mode of action of extracellular HSP27. In a previous study, we showed that intravitreal injection of HSP27 led to neuronal damage in the retina and optic nerve after 21 days. However, it was not clear which degenerative signaling pathways were induced by the injection. For this reason, the pathological mechanisms of intravitreal HSP27 injection after 14 days were investigated. Histological and RT-qPCR analyses revealed an increase in endogenous HSP27 in the retina and an activation of components of the intrinsic and extrinsic apoptosis pathway. In addition, an increase in nucleus factor-kappa-light-chain-enhancer of activated B cells (NFκB), as well as of microglia/macrophages and T-cells could be observed. In the optic nerve, however, only an increased apoptosis rate was detectable. Therefore, the activation of caspases and the induction of an incipient immune response seem to be the main triggers for retinal degeneration in this intravitreal HSP27 model.
topic glaucoma
heat shock protein 27 (HSP27)
retinal ganglion cell degeneration
apoptosis
T-cells
microglia
url https://www.mdpi.com/1422-0067/22/2/513
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