The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1‐CX3CR1 signaling in a mouse model of retinitis pigmentosa
Open accessAbstract
Retinitis pigmentosa (RP), a disease characterized by the progressive degeneration of mutation‐bearing photoreceptors, is a significant cause of incurable blindness in the young worldwide. Recent studies have found that activated retinal microglia contribute to photoreceptor demise via phagocytosis and proinflammatory factor production, however mechanisms regulating these contributions are not well‐defined. In this study, we investigate the role of CX3CR1, a microglia‐specific receptor, in regulating microglia‐mediated degeneration using the well‐established rd10 mouse model of RP. We found that in CX3CR1‐deficient (CX3CR1 GFP/GFP) rd10 mice microglial infiltration into the photoreceptor layer was significantly augmented and associated with accelerated photoreceptor apoptosis and atrophy compared with CX3CR1‐sufficient (CX3CR1 GFP/+) rd10 littermates. CX3CR1‐deficient microglia demonstrated increased phagocytosis as evidenced by (1) having increased numbers of phagosomes in vivo, (2) an increased rate of phagocytosis of fluorescent beads and photoreceptor cellular debris in vitro, and (3) increased photoreceptor phagocytosis dynamics on live cell imaging in retinal explants, indicating that CX3CR1 signaling in microglia regulates the phagocytic clearance of at‐risk photoreceptors. We also found that CX3CR1 deficiency in retinal microglia was associated with increased expression of inflammatory cytokines and microglial activation markers. Significantly, increasing CX3CL1‐CX3CR1 signaling in the rd10 retina via exogenous intravitreal delivery of recombinant CX3CL1 was effective in (1) decreasing microglial infiltration, phagocytosis and activation, and (2) improving structural and functional features of photoreceptor degeneration. These results indicate that CX3CL1‐CX3CR1 signaling is a molecular mechanism capable of modulating microglial‐mediated degeneration and represents a potential molecular target in therapeutic approaches to RP. GLIA 2016;64:1479–1491
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“…retinal microglia in photoreceptor degeneration(Zhao et al., 2015), we investigated how CX3CR1 deficiency, a key regulator of microglial physiology (Combadiere et al., 2007; Liang et al., 2009), 1482 Volume 64, No. 9 influences microglial involvement and disease progression in the rd10 model for…”
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Self-citationMicroglia-mediated degradation of perineuronal nets promotes pain
Tansley, S., Gu, N., Guzmán, A. U., Cai, W., Wong, C., Lister, K. C., Muñoz-Pino, E., Yousefpour, N., Roome, R. B., Heal, J., et al. (2022) · Science · doi:10.1126/science.abl6773 · Cited by 195
Metadata
- Authors
- Zabel, M. K., Zhao, L., Zhang, Y., Gonzalez, S. R., Ma, W., Wang, X., Fariss, R. N., & Wong, W. T.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2016-06-17
- Volume
- 64
- Issue
- 9
- Pages
- 1479-1491
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2421777402
- Cited by
- 210
- References
- 22
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zabel, M. K., Zhao, L., Zhang, Y., Gonzalez, S. R., Ma, W., Wang, X., Fariss, R. N., & Wong, W. T. (2016). Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1‐CX3CR1 signaling in a mouse model of retinitis pigmentosa. Glia. https://doi.org/10.1002/glia.23016
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