Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration.
Cell Rep
; 30(7): 2209-2224.e5, 2020 02 18.
Article
de En
| MEDLINE
| ID: mdl-32075760
ABSTRACT
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Dégénérescence de la rétine
/
Stress oxydatif
/
Récepteur de type Toll-2
Limites:
Animals
/
Humans
Langue:
En
Journal:
Cell Rep
Année:
2020
Type de document:
Article
Pays d'affiliation:
Irlande