Open AccessMicroglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration
Author(s) -
Zhao Lian,
Zabel Matthew K,
Wang Xu,
Ma Wenxin,
Shah Parth,
Fariss Robert N,
Qian Haohua,
Parkhurst Christopher N,
Gan WenBiao,
Wong Wai T
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201505298
Subject(s) - phagocytosis , retinal degeneration , degeneration (medical) , microglia , macular degeneration , retinal , biology , neuronal degeneration , retina , neuroscience , microbiology and biotechnology , medicine , pathology , immunology , inflammation , ophthalmology , disease , botany
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.