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Updated: Jul 14, 2026
In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma
Published on: May 11, 2015
Turnover of resident retinal microglia in the normal adult mouse
Heping Xu1, Mei Chen, Eric J Mayer
1Department of Ophthalmology, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. h.xu@abdn.ac.uk
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 F4/80(high)CD45(high)Iba-1(high), whereas cells in the inner and outer plexiform layers were ramified and F4/80(low) CD45(low)Iba-1(low). 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.
Insights
Bone marrow cells can replace retinal microglia and macrophages in mice, a process taking about six months. In situ proliferation mainly involves non-hematopoietic retinal cells, not microglia or macrophages.
Area of Science:
- Ophthalmology
- Immunology
- Neuroscience
Background:
- The retina harbors distinct monocyte-derived cells: perivascular macrophages and parenchymal microglia.
- These cells are crucial for retinal homeostasis, neuroinflammation, degeneration, and injury.
- The turnover and repopulation dynamics of these retinal myeloid cells remain unclear.
Purpose of the Study:
- To investigate the origin and turnover of retinal microglia and macrophages under normal physiological conditions.
- To determine if bone marrow-derived cells can repopulate the retinal myeloid cell populations.
- To elucidate the timeline and extent of bone marrow cell engraftment in the retina.
Main Methods:
- Adoptive transfer of bone marrow (BM) cells from EGFP-transgenic mice into lethally irradiated normal mice.
- Analysis of retinal flatmounts at 8, 14, and 26 weeks post-transplantation.
- Immunohistochemical identification of retinal microglia/macrophages using F4/80, CD45, and Iba-1 markers.
- Assessment of endogenous cell proliferation using Bromodeoxyuridine (BrdU) labeling.
Main Results:
- Bone marrow-derived EGFP(+) cells were detected in the retina by 8 weeks and constituted all retinal myeloid cells by 6 months post-transplantation.
- EGFP(+) cells infiltrated various retinal layers, including the peripheral retina, ganglion cell layer, inner and outer plexiform layers, and photoreceptor layer.
- In situ proliferation primarily involved non-hematopoietic retinal cells, with minimal BrdU incorporation in myeloid cell populations.
Conclusions:
- Bone marrow-derived monocyte precursor cells can migrate across the blood-retinal barrier (BRB) and replace resident retinal microglia and macrophages.
- Complete repopulation of retinal myeloid cells by donor bone marrow cells takes approximately 6 months.
- Retinal microglia and macrophages are largely maintained by continuous bone marrow-derived cell turnover rather than significant in situ proliferation.
