Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration.
2-(ω-Carboxyethyl) pyrrole
C3
C5b-C9
Complement
Membrane Attack Complex (MAC)
NaIO3
Toll-like receptor 2 (TLR2)
age-related macular degeneration (AMD)
oxidative stress
retinal degeneration
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
18 02 2020
18 02 2020
Historique:
received:
26
04
2019
revised:
18
09
2019
accepted:
21
01
2020
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
10
3
2021
Statut:
ppublish
Résumé
Retinal degeneration is a form of neurodegenerative disease and is the leading cause of vision loss globally. The Toll-like receptors (TLRs) are primary components of the innate immune system involved in signal transduction. Here we show that TLR2 induces complement factors C3 and CFB, the common and rate-limiting factors of the alternative pathway in both retinal pigment epithelial (RPE) cells and mononuclear phagocytes. Neutralization of TLR2 reduces opsonizing fragments of C3 in the outer retina and protects photoreceptor neurons from oxidative stress-induced degeneration. TLR2 deficiency also preserves tight junction expression and promotes RPE resistance to fragmentation. Finally, oxidative stress-induced formation of the terminal complement membrane attack complex and Iba1+ cell infiltration are strikingly inhibited in the TLR2-deficient retina. Our data directly implicate TLR2 as a mediator of retinal degeneration in response to oxidative stress and present TLR2 as a bridge between oxidative damage and complement-mediated retinal pathology.
Identifiants
pubmed: 32075760
pii: S2211-1247(20)30089-9
doi: 10.1016/j.celrep.2020.01.064
pmc: PMC7179253
mid: NIHMS1563624
pii:
doi:
Substances chimiques
TLR2 protein, human
0
Tlr2 protein, mouse
0
Toll-Like Receptor 2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2209-2224.e5Subventions
Organisme : NEI NIH HHS
ID : P30 EY011373
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY025580
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY016813
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.