Turnover of resident retinal microglia in the normal adult mouse

Heping Xu, Mei Chen, Eric J. Mayer, John V. Forrester, Andrew D. Dick

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

The retina contains two distinct populations of monocyte-derived cells: perivascular cells (macrophages) and parenchymal cells (microglia), important in homeostasis, neuroinflammation, degeneration, and injury. The turnover of these cells in the retina and their repopulation in normal physiological conditions have not been clarified. Bone marrow (BM) cells from EGFP-transgenic mice were adoptively transferred into lethally irradiated normal adult C57BL/6 mice. Eight, 14, and 26 weeks later mice were sacrificed and retinal flatmounts were prepared. Retinal microglia were identified by F4/80, CD45, and Iba-1 immunostaining. BrdU was injected into normal mice for 3–14 days and cell proliferation was examined by confocal microscopy of retinal flatmounts. Few (6.15 ± 2.02 cells/retina) BrdU+ cells were detected and of these some coexpressed CD11b (1.67 ± 0.62 cells/retina) or F4/80 (0.57 ± 0.30 cells/retina). BM-derived EGFP+ cells were detected by 8-weeks post-transplantation. By 6 months, all retinal myeloid cells were EGFP+. Consecutively, donor BM-EGFP+ cells were demonstrated within the: (1) peripheral and juxtapapillary retina, (2) ganglion cell layer, (3) inner and outer plexiform layers, and (4) photoreceptor layer. EGFP+ cells within the ganglion layer were amoeboid in shape and F4/80highCD45highIba-1high, whereas cells in the inner and outer plexiform layers were ramified and F4/80low CD45lowIba-1low. Perivascular macrophages expressed less F4/80, CD45, and Iba-1 compared with parenchymal microglia. Our results suggest that BM-derived monocyte precursor cells are able to migrate across the BRB and replace retinal microglia/macrophages. The complete replacement of retinal microglia/macrophages takes about 6 months. In situ proliferation was predominantly of nonhemopoetic retinal cells.
Original languageEnglish
Pages (from-to)1189-1198
Number of pages10
JournalGlia
Volume55
Issue number11
Early online date28 Jun 2007
DOIs
Publication statusPublished - 15 Aug 2007

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Microglia
Retina
Macrophages
Bromodeoxyuridine
Ganglia
Bone Marrow Cells
Monocytes
Bone Marrow
Myeloid Cells
Inbred C57BL Mouse
Confocal Microscopy
Transgenic Mice
Homeostasis
Transplantation

Keywords

  • retina
  • microglia
  • macrophage
  • bone marrow transplantation
  • experimental autoimmune uveoretinitis
  • apoptotic inflamatory cells
  • central-nervous-system
  • marrow-derived cells
  • parenchymal microglia
  • stem-cells
  • brain
  • activation
  • identification
  • proliferation

Cite this

Xu, H., Chen, M., Mayer, E. J., Forrester, J. V., & Dick, A. D. (2007). Turnover of resident retinal microglia in the normal adult mouse. Glia, 55(11), 1189-1198. https://doi.org/10.1002/glia.20535

Turnover of resident retinal microglia in the normal adult mouse. / Xu, Heping; Chen, Mei; Mayer, Eric J.; Forrester, John V.; Dick, Andrew D.

In: Glia, Vol. 55, No. 11, 15.08.2007, p. 1189-1198.

Research output: Contribution to journalArticle

Xu, H, Chen, M, Mayer, EJ, Forrester, JV & Dick, AD 2007, 'Turnover of resident retinal microglia in the normal adult mouse', Glia, vol. 55, no. 11, pp. 1189-1198. https://doi.org/10.1002/glia.20535
Xu H, Chen M, Mayer EJ, Forrester JV, Dick AD. Turnover of resident retinal microglia in the normal adult mouse. Glia. 2007 Aug 15;55(11):1189-1198. https://doi.org/10.1002/glia.20535
Xu, Heping ; Chen, Mei ; Mayer, Eric J. ; Forrester, John V. ; Dick, Andrew D. / Turnover of resident retinal microglia in the normal adult mouse. In: Glia. 2007 ; Vol. 55, No. 11. pp. 1189-1198.
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