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Macrophages during retina and optic nerve development in the mouse embryo: relationship to cell death and optic fibres

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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 (p75NTR)- and TrkA-positive. These findings suggest that macrophages may be involved in optic axon guidance and fasciculation.

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Acknowledgements

We are grateful to Dr. Pedro J. Casero and Dr. Manuel Ramírez for the use of the digital camera and microscope. We are grateful to Dr. Julio Navascués for insightful comments that helped to contribute to the final form of this manuscript. During part of this work, J.F.M. was the recipient of a grant from the Spanish Ministry of Education and Science. This work was supported by the Spanish Ministerio de Ciencia y Tecnología (PB97-0364) and the Junta de Extremadura (IPR98C028, IPR00C049).

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Authors and Affiliations

  1. Departamento de Biología Celular, Facultad de Ciencias, Universidad de Extremadura, Avda de Elvas s/n, 06071, Badajoz, Spain

    Lucía Rodríguez-Gallardo & Gervasio Martín-Partido

  2. Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Universidad de Extremadura, Avda de Elvas s/n, 06071, Badajoz, Spain

    María del Carmen Lineros-Domínguez

  3. Departamento de Biología Celular, Facultad de Veterinaria, Universidad de Extremadura, Avda de la Universidad s/n, 10071, Cáceres, Spain

    Javier Francisco-Morcillo

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  1. Lucía Rodríguez-Gallardo
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  2. María del Carmen Lineros-Domínguez
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  3. Javier Francisco-Morcillo
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  4. Gervasio Martín-Partido
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Correspondence to Gervasio Martín-Partido.

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Rodríguez-Gallardo, L., Lineros-Domínguez, M.d.C., Francisco-Morcillo, J. et al. Macrophages during retina and optic nerve development in the mouse embryo: relationship to cell death and optic fibres. Anat Embryol 210, 303–316 (2005). https://doi.org/10.1007/s00429-005-0051-3

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