scholarly journals Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1‐CX3CR1 signaling in a mouse model of retinitis pigmentosa

Glia ◽  
2016 ◽  
Vol 64 (9) ◽  
pp. 1479-1491 ◽  
Author(s):  
Matthew K. Zabel ◽  
Lian Zhao ◽  
Yikui Zhang ◽  
Shaimar R. Gonzalez ◽  
Wenxin Ma ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Degeneration ◽  
Microglial Phagocytosis

scholarly journals Carnosic acid slows photoreceptor degeneration in the Pde6brd10 mouse model of retinitis pigmentosa

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Kai Kang ◽  
Matthew J. Tarchick ◽  
Xiaoshan Yu ◽  
Craig Beight ◽  
Ping Bu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Carnosic Acid ◽  
Photoreceptor Degeneration

scholarly journals Early Microglia Activation Precedes Photoreceptor Degeneration in a Mouse Model of CNGB1-Linked Retinitis Pigmentosa

2018 ◽  
Vol 8 ◽  
Author(s):  
Thomas Blank ◽  
Tobias Goldmann ◽  
Mirja Koch ◽  
Lukas Amann ◽  
Christian Schön ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Microglia Activation ◽  
Photoreceptor Degeneration

scholarly journals Complement C3- and CR3-dependent microglial clearance protects photoreceptors in retinitis pigmentosa

2018 ◽  
Author(s):  
Sean M. Silverman ◽  
Wenxin Ma ◽  
Xu Wang ◽  
Lian Zhao ◽  
Wai T. Wong
Keyword(s):  
Retinitis Pigmentosa ◽  
Complement Activation ◽  
Complement C3 ◽  
Photoreceptor Degeneration ◽  
Therapeutic Approaches ◽  
Complement Components ◽  
Genetic Ablation ◽  
Microglial Phagocytosis

AbstractComplement activation has been implicated as an inflammatory driver of neurodegeneration in retinal and brain pathologies. However, its involvement and influence of photoreceptor degeneration in retinitis pigmentosa (RP), an inherited, largely incurable blinding disease, is unclear. We discover that markedly upregulated retinal expression of multiple complement components coincided spatiotemporally with photoreceptor degeneration in both the rd10 mouse model and in human specimens of RP, with increased complement C3 expression and activation localizing to infiltrating microglia near photoreceptors. Genetic ablation of C3 in the rd10 background resulted in accelerated structural and functional photoreceptor degeneration and altered retinal expression of inflammatory genes. These effects were phenocopied by the genetic deletion of CR3, a microglia-expressed receptor for the C3 activation product C3b, implicating an adaptive microglial-mediation mechanism involving C3-CR3 interaction. Deficiency of either C3 or CR3 resulted in deficient microglial phagocytosis of apoptotic photoreceptors in vivo, as well as increased microglial neurotoxicity to photoreceptors in vitro. These findings demonstrate a novel adaptive role for complement activation in RP that facilitates microglial clearance of apoptotic photoreceptors, without which increased proinflammatory microglial neurotoxicity ensues. These positive contributions of complement via microglial-mediated mechanisms are important in the design of immunomodulatory therapeutic approaches to neurodegeneration.One Sentence SummaryComplement activation mediates adaptive neuroprotection for photoreceptors by facilitating C3-CR3 dependent microglial clearance of apoptotic cells.

scholarly journals Luteolin delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

2021 ◽  
Vol 16 (10) ◽  
pp. 2109
Author(s):  
Ang Li ◽  
Ying Xu ◽  
Xiao-Bin Liu ◽  
Feng Liu ◽  
Yi-Yao Liang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Degeneration

scholarly journals C3- and CR3-dependent microglial clearance protects photoreceptors in retinitis pigmentosa

2019 ◽  
Vol 216 (8) ◽  
pp. 1925-1943 ◽  
Author(s):  
Sean M. Silverman ◽  
Wenxin Ma ◽  
Xu Wang ◽  
Lian Zhao ◽  
Wai T. Wong
Keyword(s):  
Retinitis Pigmentosa ◽  
Degenerative Disease ◽  
Photoreceptor Degeneration ◽  
Therapeutic Approaches ◽  
Complement Components ◽  
Inflammatory Gene Expression ◽  
Genetic Ablation ◽  
Microglial Phagocytosis ◽  
Genetic Deletion ◽  
Adaptive Role

Complement activation has been implicated as contributing to neurodegeneration in retinal and brain pathologies, but its role in retinitis pigmentosa (RP), an inherited and largely incurable photoreceptor degenerative disease, is unclear. We found that multiple complement components were markedly up-regulated in retinas with human RP and the rd10 mouse model, coinciding spatiotemporally with photoreceptor degeneration, with increased C3 expression and activation localizing to activated retinal microglia. Genetic ablation of C3 accelerated structural and functional photoreceptor degeneration and altered retinal inflammatory gene expression. These phenotypes were recapitulated by genetic deletion of CR3, a microglia-expressed receptor for the C3 activation product iC3b, implicating C3-CR3 signaling as a regulator of microglia–photoreceptor interactions. Deficiency of C3 or CR3 decreased microglial phagocytosis of apoptotic photoreceptors and increased microglial neurotoxicity to photoreceptors, demonstrating a novel adaptive role for complement-mediated microglial clearance of apoptotic photoreceptors in RP. These homeostatic neuroinflammatory mechanisms are relevant to the design and interpretation of immunomodulatory therapeutic approaches to retinal degenerative disease.

Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa

2017 ◽  
Vol 63 (3) ◽  
pp. e12428 ◽  
Author(s):  
Xiao-Jian Xu ◽  
Shu-Min Wang ◽  
Ying Jin ◽  
Yun-Tao Hu ◽  
Kang Feng ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Photoreceptor Degeneration

scholarly journals Lutein delays photoreceptor degeneration in a mouse model of retinitis pigmentosa

2022 ◽  
Vol 17 (7) ◽  
pp. 1596
Author(s):  
Ying Xu ◽  
Xue-Song Mi ◽  
Shi-Bo Tang ◽  
Hui-Jun Zhang ◽  
Xiao-Bin Liu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Photoreceptor Degeneration

scholarly journals Temporal Contrast Sensitivity Increases Despite Photoreceptor Degeneration in a Mouse Model of Retinitis Pigmentosa

eNeuro ◽  
2021 ◽  
pp. ENEURO.0020-21.2021
Author(s):  
Rose L. Pasquale ◽  
Ying Guo ◽  
Yumiko Umino ◽  
Barry Knox ◽  
Eduardo Solessio
Keyword(s):  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Contrast Sensitivity ◽  
Photoreceptor Degeneration ◽  
Temporal Contrast

scholarly journals Photoreceptor degeneration changes magnetic resonance imaging features in a mouse model of retinitis pigmentosa

2011 ◽  
Vol 65 (6) ◽  
pp. 1793-1798 ◽  
Author(s):  
Qing Wang ◽  
Sheng-Kwei Song ◽  
Huiying Zhang ◽  
Bruce A. Berkowitz ◽  
Shiming Chen ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Mouse Model ◽  
Retinitis Pigmentosa ◽  
Imaging Features ◽  
Photoreceptor Degeneration ◽  
Resonance Imaging
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