Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner

Abstract Retinal degeneration is a common cause of irreversible blindness and is caused by the death of retinal light-sensitive neurons called photoreceptors. At the onset of degeneration, stressed photoreceptors cause retinal glial cells to secrete neuroprotective factors that slow the pace of dege...

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Autores principales:	Marcus J. Hooper, Jiangang Wang, Robert Browning, John D. Ash
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d7b55eaf54594d6dae1bfe7115a90f6e
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spelling	oai:doaj.org-article:d7b55eaf54594d6dae1bfe7115a90f6e2021-12-02T11:40:46ZDamage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner10.1038/s41598-018-27479-x2045-2322https://doaj.org/article/d7b55eaf54594d6dae1bfe7115a90f6e2018-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-27479-xhttps://doaj.org/toc/2045-2322Abstract Retinal degeneration is a common cause of irreversible blindness and is caused by the death of retinal light-sensitive neurons called photoreceptors. At the onset of degeneration, stressed photoreceptors cause retinal glial cells to secrete neuroprotective factors that slow the pace of degeneration. Leukemia inhibitory factor (LIF) is one such factor that is required for endogenous neuroprotection. Photoreceptors are known to release signals of cellular stress, called damage-associated molecular patterns (DAMPs) early in degeneration, and we hypothesized that receptors for DAMPs or pattern recognition receptors (PRRs) play a key role in the induction of LIF and neuroprotective stress responses in retinal glial cells. Toll-like receptor 2 (TLR2) is a well-established DAMP receptor. In our experiments, activation of TLR2 protected both male and female mice from light damage, while the loss of TLR2 in female mice did not impact photoreceptor survival. In contrast, induction of protective stress responses, microglial phenotype and photoreceptor survival were strongly impacted in male TLR2−/− mice. Lastly, using publicly available gene expression data, we show that TLR2 is expressed highly in resting microglia prior to injury, but is also induced in Müller cells in inherited retinal degeneration.Marcus J. HooperJiangang WangRobert BrowningJohn D. AshNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marcus J. Hooper Jiangang Wang Robert Browning John D. Ash Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner
description	Abstract Retinal degeneration is a common cause of irreversible blindness and is caused by the death of retinal light-sensitive neurons called photoreceptors. At the onset of degeneration, stressed photoreceptors cause retinal glial cells to secrete neuroprotective factors that slow the pace of degeneration. Leukemia inhibitory factor (LIF) is one such factor that is required for endogenous neuroprotection. Photoreceptors are known to release signals of cellular stress, called damage-associated molecular patterns (DAMPs) early in degeneration, and we hypothesized that receptors for DAMPs or pattern recognition receptors (PRRs) play a key role in the induction of LIF and neuroprotective stress responses in retinal glial cells. Toll-like receptor 2 (TLR2) is a well-established DAMP receptor. In our experiments, activation of TLR2 protected both male and female mice from light damage, while the loss of TLR2 in female mice did not impact photoreceptor survival. In contrast, induction of protective stress responses, microglial phenotype and photoreceptor survival were strongly impacted in male TLR2−/− mice. Lastly, using publicly available gene expression data, we show that TLR2 is expressed highly in resting microglia prior to injury, but is also induced in Müller cells in inherited retinal degeneration.
format	article
author	Marcus J. Hooper Jiangang Wang Robert Browning John D. Ash
author_facet	Marcus J. Hooper Jiangang Wang Robert Browning John D. Ash
author_sort	Marcus J. Hooper
title	Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner
title_short	Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner
title_full	Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner
title_fullStr	Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner
title_full_unstemmed	Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner
title_sort	damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/d7b55eaf54594d6dae1bfe7115a90f6e
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Damage-associated molecular pattern recognition is required for induction of retinal neuroprotective pathways in a sex-dependent manner

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