Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration.

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Mulfaul K,Ozaki E,Fernando N,Brennan K,Chirco KR,Connolly E,Greene C,Maminishkis A,Salomon RG,Linetsky M,Natoli R,Mullins RF,Campbell M,Doyle SL

doi

10.1016/j.celrep.2020.01.064

subject

Has Abstract

pub_date

2020-02-18 00:00:00

pages

2209-2224.e5

issue

7

issn

2211-1247

pii

S2211-1247(20)30089-9

journal_volume

30

pub_type

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