Expression of inducible heat shock proteins Hsp27 and Hsp70 in the visual pathway of rats subjected to various models of retinal ganglion cell injury.

Glyn Chidlow,John P M Wood,Robert J Casson,Marta Agudo-Barriuso

doi:10.1371/journal.pone.0114838

Glyn Chidlow, John P M Wood + Show 2 more

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https://doi.org/10.1371/journal.pone.0114838

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Journal: PloS one	Publication Date: Dec 23, 2014
Citations: 41	License type: CC BY 4.0

Affiliation: Hanson Institute, University of Adelaide

Abstract

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and −70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and −70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration.

Highlights

One mechanism by which mammalian cells respond to pathophysiological stress is via the synthesis of highly conserved molecular chaperones termed heat shock proteins (Hsps)
Tissue sections from rats subjected to focal ischemia were employed in this study for two reasons: Firstly, transient MCAO is well-known to cause a pronounced induction of both Hsp27 and Hsp70 in the affected hemisphere [32, 33]
Double labelling immunofluorescence confirmed that Hsp27 expression colocalised with GFAP-labelled astrocytes, while Hsp70 colocalised to NeuN-labelled neurons

Summary

Introduction

One mechanism by which mammalian cells respond to pathophysiological stress is via the synthesis of highly conserved molecular chaperones termed heat shock proteins (Hsps) These inducible proteins confer cellular protection against ongoing and subsequent insults, as well as contributing to cellular repair mechanisms [1]. Induction of both Hsp and 270 occurs within defined spatial and temporal parameters in response to various pathological conditions, including, but by no means restricted, to ischemia, excitotoxicity and axonal injury [2]. These Hsps are increasingly viewed as ideal candidates to serve as biomarkers to identify near-lethal stress associated with pathological conditions in the brain [3]. In terms of the cell types involved in each response, Hsp is principally upregulated by astrocytes, while Hsp is classically expressed by neurons [2]

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