Microglial Phagocytosis of Living Photoreceptors Contributes to Inherited Retinal Degeneration

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2015 Jul 4

PMID 26139610

Citations 252

Authors

Lian Zhao

Matthew K Zabel

Xu Wang

Wenxin Ma

Parth Shah

Robert N Fariss

Haohua Qian

Christopher N Parkhurst

Wen-Biao Gan

Wai T Wong

Affiliations

Soon will be listed here.

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.

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