ArticleJournal of molecular neuroscience : MN2020
Increased Neuroprotective Microglia and Photoreceptor Survival in the Retina from a Peptide Inhibitor of Myeloid Differentiation Factor 88 (MyD88).
Article in Journal of molecular neuroscience : MN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 31 citations in OpenAlex.
- CCR1 signaling as a common injury pathway in retinal degeneration.Journal of neuroinflammation · 2026Article
- Myd88 Deficiency Accelerates Retinal Degeneration and Alters Microglial Dynamics in a Mouse Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Chronic exposure to aerosolized Arizona test dust reduces visual acuity in mice.Toxicology reports · 2026Article
- The Effects of Lead, Cadmium and Arsenic Exposure Alone or in Combination on Neurotoxicity Through Neural Signaling Pathways.Biological trace element research · 2026Review
- Cellular responses of human Muller glia exposed to test dust pollution.Environmental pollution (Barking, Essex : 1987) · 2026Article
- Interleukin 27-induced photoreceptor survival is associated with suppression of a novel Muller glia subpopulation.Cell communication and signaling : CCS · 2026Article
- Identifying a role for oxytosis/ferroptosis in Pde6b-associated retinitis pigmentosa.Experimental eye research · 2025Article
- Research status and future perspectives of IL‑27 in the treatment of stroke (Review).International journal of molecular medicine · 2025Review
- Evaluating the Evidence for Neuroprotective and Axonal Regenerative Activities of Different Inflammatory Cell Types After Optic Nerve Injury.Molecular neurobiology · 2025Review
- Article
- TLR2 and TLR4 Are Expressed in Epiretinal Membranes: Possible Links with Vitreous Levels of Complement Fragments and DAMP-Related Proteins.International journal of molecular sciences · 2024Article
- The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome.Journal of neuroinflammation · 2024Review
- Immunology of Retinitis Pigmentosa and Gene Therapy-Associated Uveitis.Cold Spring Harbor perspectives in medicine · 2024Review
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.Investigative ophthalmology & visual science · 2023Article
- Article
- Assessment of outer retinal thickness and function in mice after experimental optic nerve trauma.BMC ophthalmology · 2022Article
- Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases.Neural regeneration research · 2022Review
- The cytokine IL-27 reduces inflammation and protects photoreceptors in a mouse model of retinal degeneration.Journal of neuroinflammation · 2022Article
- Photoreceptor Cells Constitutively Express IL-35 and Promote Ocular Immune Privilege.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Myeloid differentiation factor 88 (MyD88) is an adaptor protein for the Toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) families of innate immunity receptors that mediate inflammatory responses to cellular injury. TLR/IL1R/MyD88 signaling is known to contribute to retinal degeneration, although how MyD88 regulates neuronal survival, and the effect of MyD88 on the inflammatory environment in the retina, is mostly unknown. In this study, we tested the hypothesis that blocking MyD88-mediated signaling early in retinal degeneration promotes transition of microglia towards a neuroprotective anti-inflammatory phenotype, resulting in enhanced photoreceptor survival. We also tested whether systemic delivery of a pharmacologic MyD88 inhibitor has therapeutic potential. The rd10 mouse model of retinal degeneration was injected intraperitoneally with increasing doses of a MyD88 blocking peptide or control peptide early in degeneration, and inflammatory responses and photoreceptor survival were measured at specific time points using flow cytometry, cytokine profiling, and electroretinograms. Our results demonstrated that rd10 mice injected with a low dose of MyD88 inhibitor peptide showed increased rod photoreceptor function and reduced apoptosis compared with control peptide and uninjected mice. MyD88 inhibition also resulted in fewer microglia/macrophage cells in the photoreceptor layer whereas total peripheral and retinal macrophage were not changed. Furthermore, increased number of cells expressing the Arg1 marker of neuroprotective microglia in the photoreceptor layer and higher MCP-1 and anti-inflammatory cytokine IL-27 were associated with photoreceptor survival. Therefore, these data suggest that the MyD88 inhibitor modified the retina environment to become less inflammatory, leading to improved photoreceptor function and survival.
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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.