| Autor: |
Kelly Mulfaul, Ema Ozaki, Nilisha Fernando, Kiva Brennan, Kathleen R. Chirco, Emma Connolly, Chris Greene, Arvydas Maminishkis, Robert G. Salomon, Mikhail Linetsky, Riccardo Natoli, Robert F. Mullins, Matthew Campbell, Sarah L. Doyle |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 30, Iss 7, Pp 2209-2224.e5 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2020.01.064 |
| Popis: |
Summary: 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. : Oxidative stress and complement deposition are common to many retinal degenerative diseases. Mulfaul et al. demonstrate that TLR2 blockade protects against photoreceptor neuronal cell death and RPE fragmentation in experimental models of oxidative stress-induced retinal degeneration and present TLR2 as a bridge between oxidative damage and complement-mediated retinal pathology. Keywords: Toll-like receptor 2 (TLR2), Complement, Membrane Attack Complex (MAC), oxidative stress, 2-(ω-Carboxyethyl) pyrrole, C3, C5b-C9, age-related macular degeneration (AMD), retinal degeneration, NaIO3 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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