Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720300899 |
| _version_ | 1819083061167390720 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kelly Mulfaul |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-21T20:26:34Z |
| format | Article |
| id | doaj.art-835c88f2ea654e568ca728ae96a0f4bf |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-21T20:26:34Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-835c88f2ea654e568ca728ae96a0f4bf2022-12-21T18:51:21ZengElsevierCell Reports2211-12472020-02-0130722092224.e5Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal DegenerationKelly Mulfaul0Ema Ozaki1Nilisha Fernando2Kiva Brennan3Kathleen R. Chirco4Emma Connolly5Chris Greene6Arvydas Maminishkis7Robert G. Salomon8Mikhail Linetsky9Riccardo Natoli10Robert F. Mullins11Matthew Campbell12Sarah L. Doyle13Department Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, IrelandDepartment Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, IrelandThe John Curtin School of Medical Research, The Australian National University, Canberra, ACT, AustraliaDepartment Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, IrelandInstitute for Vision Research, University of Iowa, Iowa City, IA, USADepartment Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, IrelandSmurfit Institute of Genetics, Trinity College Dublin, Dublin, IrelandNational Eye Institute, National Institutes of Health, Bethesda, MD, USADepartment of Chemistry, Case Western Reserve University, Cleveland, OH, USADepartment of Chemistry, Case Western Reserve University, Cleveland, OH, USAThe John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia; The ANU Medical School, The Australian National University, Canberra, ACT, AustraliaInstitute for Vision Research, University of Iowa, Iowa City, IA, USASmurfit Institute of Genetics, Trinity College Dublin, Dublin, IrelandDepartment Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland; Trinity College Institute of Neuroscience (TCIN), TCD, Dublin 2, Ireland; The National Children’s Research Centre, Our Lady’s Hospital Crumlin, Dublin 12, Ireland; Corresponding authorSummary: 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, NaIO3http://www.sciencedirect.com/science/article/pii/S2211124720300899 |
| spellingShingle | 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 Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration Cell Reports |
| title | Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration |
| title_full | Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration |
| title_fullStr | Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration |
| title_full_unstemmed | Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration |
| title_short | Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration |
| title_sort | toll like receptor 2 facilitates oxidative damage induced retinal degeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720300899 |
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