RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury

Seyed Hosseini Fin, N; Georgevsky, D; Sukkar, MB; Golzan, SM

RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury

Seyed Hosseini Fin, N Georgevsky, D Sukkar, MB Golzan, SM

Permalink

Publisher:: Frontiers Media SA
Publication Type:: Journal Article
Citation:: Frontiers in Cellular Neuroscience, 17

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Published versionAdobe PDF (3.73 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Seyed Hosseini Fin, N
dc.contributor.author	Georgevsky, D
dc.contributor.author	Sukkar, MB
dc.contributor.author	Golzan, SM
dc.date.accessioned	2023-04-13T23:10:11Z
dc.date.available	2023-04-13T23:10:11Z
dc.identifier.citation	Frontiers in Cellular Neuroscience, 17
dc.identifier.issn	1662-5102
dc.identifier.uri	http://hdl.handle.net/10453/169785
dc.description.abstract	<jats:sec><jats:title>Introduction</jats:title><jats:p>Glaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand Aß, have been shown to mediate neuronal loss <jats:italic>via</jats:italic> internalizing Aß within the neurons. In this study, we investigated whether the RAGE–Aß axis plays a role in RGC loss in experimental glaucoma.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Retinal ischemia was induced by an acute elevation of intraocular pressure in RAGE<jats:sup>–/–</jats:sup> and wild-type (WT) control mice. In a subset of animals, oligomeric Aß was injected directly into the vitreous of both strains. RGC loss was assessed using histology and biochemical assays. Baseline and terminal positive scotopic threshold (pSTR) were also recorded.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Retinal ischemia resulted in 1.9-fold higher RGC loss in WT mice compared to RAGE<jats:sup>–/–</jats:sup> mice (36 ± 3% <jats:italic>p</jats:italic> &lt; 0.0001 vs. 19 ± 2%, <jats:italic>p</jats:italic> = 0.004). Intravitreal injection of oligomeric Aß resulted in 2.3-fold greater RGC loss in WT mice compared to RAGE<jats:sup>–/–</jats:sup> mice, 7-days post-injection (55 ± 4% <jats:italic>p</jats:italic> = 0.008 vs. 24 ± 2%, <jats:italic>p</jats:italic> = 0.02). We also found a significant decline in the positive scotopic threshold response (pSTR) amplitude of WT mice compared to RAGE<jats:sup>–/–</jats:sup> (36 ± 3% vs. 16 ± 6%).</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>RAGE<jats:sup>–/–</jats:sup> mice are protected against RGC loss following retinal ischemia. Intravitreal injection of oligomeric Aß accelerated RGC loss in WT mice but not RAGE<jats:sup>–/–</jats:sup>. A co-localization of RAGE and Aß, suggests that RAGE–Aß binding may contribute to RGC loss.</jats:p></jats:sec>
dc.language	en
dc.publisher	Frontiers Media SA
dc.relation	http://purl.org/au-research/grants/nhmrc/1105930
dc.relation	ANZ Trustees Limited
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1105930
dc.relation.ispartof	Frontiers in Cellular Neuroscience
dc.relation.isbasedon	10.3389/fncel.2023.1156084
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1109 Neurosciences
dc.title	RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury
dc.type	Journal Article
utslib.citation.volume	17
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1109 Neurosciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Orthoptics
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2023-04-13T23:10:09Z
pubs.publication-status	Published online
pubs.volume	17

Abstract:

IntroductionGlaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand Aß, have been shown to mediate neuronal loss via internalizing Aß within the neurons. In this study, we investigated whether the RAGE–Aß axis plays a role in RGC loss in experimental glaucoma.MethodsRetinal ischemia was induced by an acute elevation of intraocular pressure in RAGE–/– and wild-type (WT) control mice. In a subset of animals, oligomeric Aß was injected directly into the vitreous of both strains. RGC loss was assessed using histology and biochemical assays. Baseline and terminal positive scotopic threshold (pSTR) were also recorded.ResultsRetinal ischemia resulted in 1.9-fold higher RGC loss in WT mice compared to RAGE–/– mice (36 ± 3% p < 0.0001 vs. 19 ± 2%, p = 0.004). Intravitreal injection of oligomeric Aß resulted in 2.3-fold greater RGC loss in WT mice compared to RAGE–/– mice, 7-days post-injection (55 ± 4% p = 0.008 vs. 24 ± 2%, p = 0.02). We also found a significant decline in the positive scotopic threshold response (pSTR) amplitude of WT mice compared to RAGE–/– (36 ± 3% vs. 16 ± 6%).DiscussionRAGE–/– mice are protected against RGC loss following retinal ischemia. Intravitreal injection of oligomeric Aß accelerated RGC loss in WT mice but not RAGE–/–. A co-localization of RAGE and Aß, suggests that RAGE–Aß binding may contribute to RGC loss.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/169785