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An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival
Published on: April 25, 2011
Macrophages during retina and optic nerve development in the mouse embryo: relationship to cell death and optic
Lucía Rodríguez-Gallardo1, María del Carmen Lineros-Domínguez, Javier Francisco-Morcillo
1Departamento de Biología Celular, Facultad de Ciencias, Universidad de Extremadura, Avda de Elvas s/n, 06071, Badajoz, Spain. lrguez@unex.es
Abstract:
We compared the spatial and temporal patterns of distribution of macrophages, with patterns of naturally occurring cell death and optic fibre growth during early retina and optic nerve development, in the mouse. We used embryos between day 10 of embryogenesis (E10; before the first optic fibres are generated in the retina) and E13 (when the first optic fibres have crossed the chiasmatic anlage). The macrophages and optic axons were identified by immunocytochemistry, and the apoptotic cells were detected by the TUNEL technique, which specifically labels fragmented DNA. Cell death was observed in the retina and the optic stalk long before the first optic axons appeared in either region. Subsequently, specialized F4/80-positive phagocytes were detected in chronological and topographical coincidence with cell death, which disappeared progressively. As development proceeded, the pioneer ganglion cell axons reached the regions where the macrophages were located. As the number of optic fibres increased, the macrophages disappeared. Therefore, cell death, accompanied by macrophages, preceded the growth of fibres in the retina and the optic nerve. Moreover, these macrophages synthesized NGF and the optic axons were p75 neurotrophin receptor (p75(NTR))- and TrkA-positive. These findings suggest that macrophages may be involved in optic axon guidance and fasciculation.
Insights
Macrophages and cell death precede optic nerve development in mice. These findings suggest macrophages play a role in guiding optic nerve fibers during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Early development of the retina and optic nerve involves complex cellular processes.
- Understanding the interplay between immune cells and neuronal development is crucial.
Purpose of the Study:
- To investigate the spatial and temporal relationship between macrophages, cell death, and optic fiber growth during mouse embryonic development.
- To explore the potential role of macrophages in optic nerve guidance.
Main Methods:
- Used mouse embryos from embryonic day 10 (E10) to E13.
- Employed immunocytochemistry to identify macrophages and optic axons.
- Utilized the TUNEL technique to detect apoptotic cells.
Main Results:
- Observed significant cell death in the retina and optic stalk before optic axons appeared.
- F4/80-positive macrophages coincided with cell death and disappeared as optic fibers grew.
- Macrophages synthesized nerve growth factor (NGF), and optic axons expressed relevant receptors (p75(NTR) and TrkA).
Conclusions:
- Cell death and associated macrophages precede optic fiber growth in the developing retina and optic nerve.
- Macrophages may actively participate in guiding and fasciculating optic axons.
- This suggests a novel role for macrophages in neural development and guidance pathways.
