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Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin

Nature Neuroscience volume 6, pages 863–868 (2003)Cite this article

Abstract

With recent progress in neuroscience and stem-cell research, neural transplantation has emerged as a promising therapy for treating CNS diseases. The success of transplantation has been limited, however, by the restricted ability of neural implants to survive and establish neuronal connections with the host. Little is known about the mechanisms responsible for this failure. Neural implantation triggers reactive gliosis, a process accompanied by upregulation of intermediate filaments in astrocytes and formation of astroglial scar tissue. Here we show that the retinas of adult mice deficient in glial fibrillary acidic protein and vimentin, and consequently lacking intermediate filaments in reactive astrocytes and Müller cells, provide a permissive environment for grafted neurons to migrate and extend neurites. The transplanted cells integrated robustly into the host retina with distinct neuronal identity and appropriate neuronal projections. Our results indicate an essential role for reactive astroglial cells in preventing neural graft integration after transplantation.

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Figure 1: Failure of graft integration and induction of reactive gliosis after retinal transplantation in wild-type mice.
Figure 2: Robust neural graft integration into the retina of adult GFAP−/−Vim−/− mice.
Figure 3: Morphological integration of EGFP neurons into the GCL of GFAP−/−Vim−/− mice.
Figure 4: Morphological integration of transplanted cells into the retinas of adult GFAP−/−Vim−/− mice.
Figure 5: Neuronal repopulation and integration in the retinas of wild-type (WT), GFAP−/−Vim−/− (GV), GFAP−/−(G), and Vim−/− (V) mice.
Figure 6: Morphology of reactive astrocytes, Müller glial cells and the ILM in the retinas of GFAP−/−Vim−/− mice.

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Acknowledgements

We thank B. Pawlyk and T. Li for conducting mouse retinal ERGs, D.W. Pottle for confocal microscopy and M. Young and C.L. Barnstable for critical discussion. This work was supported by grants from the National Eye Institute (EY012983), the Lilly Foundation for Aging Research, the Juvenile Diabetes Research Foundation, the Massachusetts Lion's Eye Research Fund and the Minda de GunzBurg Research Center for Retinal Transplantation at the Schepens Eye Research Institute (to D.F.C.) and by grants from the Swedish Cancer Foundation, the Swedish Medical Research Council, the Swedish Society for Medicine, the Swedish Society for Medical Research, the King Gustaf V Foundation, Volvo Assar Gabrielsson Fond and the Swedish Stroke Foundation (to M.P.).

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  1. Milos Pekny and Dong Feng Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Schepens Eye Research Institute and Department of Ophthalmology, Program in Neuroscience, Harvard Medical School, 20 Staniford Street, Boston, 02114, Massachusetts, USA

    Reiko Kinouchi, Masumi Takeda, Liu Yang & Dong Feng Chen

  2. Department of Medical Biochemistry, Göteborg University, Medicinaregatan 9A, Göteborg, SE-413 90, Sweden

    Ulrika Wilhelmsson, Andrea Lundkvist & Milos Pekny

  3. Department of Ophthalmology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa, 078-8510, Japan

    Masumi Takeda

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  1. Reiko Kinouchi
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Correspondence to Milos Pekny or Dong Feng Chen.

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Kinouchi, R., Takeda, M., Yang, L. et al. Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat Neurosci 6, 863–868 (2003). https://doi.org/10.1038/nn1088

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