ArticleThe Journal of biological chemistry2013
Photoreceptor proteins initiate microglial activation via Toll-like receptor 4 in retinal degeneration mediated by all-trans-retinal.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
What it found
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The trial behind it
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Who cites it
118 citing papers in PubMed, 177 citations in OpenAlex.
- Management of cystoid macular edema secondary to retinitis pigmentosa via subliminal micropulse yellow laser.Lasers in medical science · 2021Trial
- Putative mechanisms of ocular inflammation in syphilis.Journal of ophthalmic inflammation and infection · 2026Review
- Photoreceptor outer segments promote the accumulation of lipid droplets in microglia by reprogramming lipid metabolism.Frontiers in immunology · 2026Article
- Minocycline treatment reduces the activation of mononuclear phagocytes and improves retinal function in a mouse model of Leber congenital amaurosis.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Article
- Identifying a role for oxytosis/ferroptosis in Pde6b-associated retinitis pigmentosa.Experimental eye research · 2025Article
- Sustained release of a novel non-fibrate PPARα agonist from microparticles for neuroprotection in murine models of age-related macular degeneration.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Clearing the AIR: AAmerican journal of ophthalmology case reports · 2025Article
- Light as a Mediator of Acute and Chronic Retina Degeneration.Advances in experimental medicine and biology · 2025Review
- Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity.Frontiers in immunology · 2025Review
- Deciphering the role of oleic acid in diabetic retinopathy: an empirical analysis of monounsaturated fatty acids.Nutrition & metabolism · 2024Article
- Quercetin Regulates Microglia M1/M2 Polarization and Alleviates Retinal Inflammation via ERK/STAT3 Pathway.Inflammation · 2024Article
- Ocular and Serum Profiles of Inflammatory Molecules Associated With Retinitis Pigmentosa.Translational vision science & technology · 2024Article
- Review
- Hyperoside mitigates photoreceptor degeneration in part by targeting cGAS and suppressing DNA-induced microglial activation.Acta neuropathologica communications · 2024Article
- Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2.The Journal of experimental medicine · 2024Article
- Review
- Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration.Journal of neuroinflammation · 2024Article
- Immunology of Retinitis Pigmentosa and Gene Therapy-Associated Uveitis.Cold Spring Harbor perspectives in medicine · 2024Review
- Scavenging of Cation Radicals of the Visual Cycle Retinoids by Lutein, Zeaxanthin, Taurine, and Melanin.International journal of molecular sciences · 2023Article
- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (Basel, Switzerland) · 2023Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Although several genetic and biochemical factors are associated with the pathogenesis of retinal degeneration, it has yet to be determined how these different impairments can cause similar degenerative phenotypes. Here, we report microglial/macrophage activation in both a Stargardt disease and age-related macular degeneration mouse model caused by delayed clearance of all-trans-retinal from the retina, and in a retinitis pigmentosa mouse model with impaired retinal pigment epithelium (RPE) phagocytosis. Mouse microglia displayed RPE cytotoxicity and increased production of inflammatory chemokines/cytokines, Ccl2, Il1b, and Tnf, after coincubation with ligands that activate innate immunity. Notably, phagocytosis of photoreceptor proteins increased the activation of microglia/macrophages and RPE cells isolated from model mice as well as wild-type mice. The mRNA levels of Tlr2 and Tlr4, which can recognize proteins as their ligands, were elevated in mice with retinal degeneration. Bone marrow-derived macrophages from Tlr4-deficient mice did not increase Ccl2 after coincubation with photoreceptor proteins. Tlr4(-/-)Abca4(-/-)Rdh8(-/-) mice displayed milder retinal degenerative phenotypes than Abca4(-/-)Rdh8(-/-) mice. Additionally, inactivation of microglia/macrophages by pharmacological approaches attenuated mouse retinal degeneration. This study demonstrates an important contribution of TLR4-mediated microglial activation by endogenous photoreceptor proteins in retinal inflammation that aggravates retinal cell death. This pathway is likely to represent an underlying common pathology in degenerative retinal disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.