June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Microglia homeostasis in the adult mouse retina: restoration of microglial distribution, morphology, and function following acute depletion
Author Affiliations & Notes
  • Yikui Zhang
    National Eye Institute, Bethesda, Maryland, United States
  • Lian Zhao
    National Eye Institute, Bethesda, Maryland, United States
  • Xu Wang
    National Eye Institute, Bethesda, Maryland, United States
  • Wenxin Ma
    National Eye Institute, Bethesda, Maryland, United States
  • Adam Lazere
    National Eye Institute, Bethesda, Maryland, United States
  • Haohua Qian
    National Eye Institute, Bethesda, Maryland, United States
  • Robert N Fariss
    National Eye Institute, Bethesda, Maryland, United States
  • Jun Zhang
    National Eye Institute, Bethesda, Maryland, United States
  • Mones S Abu-Asab
    National Eye Institute, Bethesda, Maryland, United States
  • Wai T Wong
    National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Yikui Zhang, None; Lian Zhao, None; Xu Wang, None; Wenxin Ma, None; Adam Lazere, None; Haohua Qian, None; Robert Fariss, None; Jun Zhang, None; Mones Abu-Asab, None; Wai Wong, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 806. doi:
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    • Get Citation

      Yikui Zhang, Lian Zhao, Xu Wang, Wenxin Ma, Adam Lazere, Haohua Qian, Robert N Fariss, Jun Zhang, Mones S Abu-Asab, Wai T Wong; Microglia homeostasis in the adult mouse retina: restoration of microglial distribution, morphology, and function following acute depletion. Invest. Ophthalmol. Vis. Sci. 2017;58(8):806.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Microglia are long-lived resident innate immune cells that are found as ramified cells distributed across the retina in a regularly tiled pattern. The factors that maintain the organization of retinal microglia are not understood. We investigate how microglia undergo repopulation in the retina following acute depletion and examine the origin and function of “new” repopulating microglia.

Methods : Two models for microglial depletion were used: (1) a genetic model involving tamoxifen-induced microglial-specific expression of diphtheria toxin (DTA) subunit alpha, and (2) a pharmacological model involving PLX5622, a small molecule antagonist of CSF1R whose signaling is required for microglial viability. Microglia repopulation following depletion was monitored with in vivo retinal imaging, fate mapping technology, and Iba1 immunohistochemistry. Characterization of repopulating microglia and their effects in the retina were performed using ex vivo live cell imaging, electroretinography (ERG), electron microscopy (EM) and immunohistochemistry.

Results : In both depletion models, Iba1+ microglia repopulated the retina following short-term depletion of endogenous retinal microglia. Initial repopulating cells emerged primarily in the peripapillary region in the inner plexiform layer (IPL) of the retina, subsequently spreading over the entire retina. Early repopulating microglia are small and simple, but increase progressively in ramification to fully recapitulate original microglial morphology. Time-lapse in vivo fundus imaging demonstrated prominent cell migration and division in repopulating microglia. Fate mapping of endogenous microglia indicated that repopulating microglia originated mostly from the few residual microglia remaining after depletion. Repleted microglia demonstrated similar functions as endogenous microglia in terms of: (1) surveillance process motility, (2) response to light injury, and (3) maintenance of retinal synapse structure and function as evaluated by ERG and EM analysis.

Conclusions : Homeostasis exists in the retina to facilitate a robust repopulation of microglia following depletion that fully and precisely restores the original numbers, distribution, morphology and functions of endogenous microglia via cellular division, migration of residual microglia.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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