Abstract:
:Retinitis pigmentosa, caused predominantly by mutations in photoreceptor genes, currently lacks comprehensive treatment. We discover that retinal microglia contribute non-cell autonomously to rod photoreceptor degeneration by primary phagocytosis of living rods. Using rd10 mice, we found that the initiation of rod degeneration is accompanied by early infiltration of microglia, upregulation of phagocytic molecules in microglia, and presentation of "eat-me" signals on mutated rods. On live-cell imaging, infiltrating microglia interact dynamically with photoreceptors via motile processes and engage in rapid phagocytic engulfment of non-apoptotic rods. Microglial contribution to rod demise is evidenced by morphological and functional amelioration of photoreceptor degeneration following genetic ablation of retinal microglia. Molecular inhibition of microglial phagocytosis using the vitronectin receptor antagonist cRGD also improved morphological and functional parameters of degeneration. Our findings highlight primary microglial phagocytosis as a contributing mechanism underlying cell death in retinitis pigmentosa and implicate microglia as a potential cellular target for therapy.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Zhao L,Zabel MK,Wang X,Ma W,Shah P,Fariss RN,Qian H,Parkhurst CN,Gan WB,Wong WTdoi
10.15252/emmm.201505298subject
Has Abstractpub_date
2015-09-01 00:00:00pages
1179-97issue
9eissn
1757-4676issn
1757-4684pii
emmm.201505298journal_volume
7pub_type
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