May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Potential for neural regeneration following neurotoxic injury in the adult mammalian retina
Author Affiliations & Notes
  • S. Ooto
    Ophthalmology & Vis Sci,
    Kyoto Univ Grad Med Sch, Kyoto, Japan
  • T. Akagi
    Ophthalmology & Vis Sci,
    Kyoto Univ Grad Med Sch, Kyoto, Japan
  • R. Kageyama
    Virus Research,
    Kyoto Univ Grad Med Sch, Kyoto, Japan
  • J. Akita
    Ophthalmology & Vis Sci,
    Kyoto Univ Grad Med Sch, Kyoto, Japan
  • M. Mandai
    Ophthalmology & Vis Sci,
    Kyoto Univ Grad Med Sch, Kyoto, Japan
    Experimental Therapeutics, Translatinal Reseach Center, Kyoto Univ Hospital, Kyoto, Japan
  • Y. Honda
    Ophthalmology & Vis Sci,
    Kyoto Univ Grad Med Sch, Kyoto, Japan
  • M. Takahashi
    Ophthalmology & Vis Sci,
    Kyoto Univ Grad Med Sch, Kyoto, Japan
    Experimental Therapeutics, Translatinal Reseach Center, Kyoto Univ Hospital, Kyoto, Japan
  • Footnotes
    Commercial Relationships  S. Ooto, None; T. Akagi, None; R. Kageyama, None; J. Akita, None; M. Mandai, None; Y. Honda, None; M. Takahashi, None.
  • Footnotes
    Support  MEXT
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 5415. doi:
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    • Get Citation

      S. Ooto, T. Akagi, R. Kageyama, J. Akita, M. Mandai, Y. Honda, M. Takahashi; Potential for neural regeneration following neurotoxic injury in the adult mammalian retina . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5415.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose:It has been long believed that the retina of mature mammals is incapable of regeneration. However, here we show that Muller glia of adult mammals could be progenitor–like cells, and generate new retinal neurons. Methods:N–methyl–D–aspartate (NMDA) was injected into the vitreous chamber of adult rat (postnatal 6–7 weeks) eyes to induce neurotoxic injury. We injected bromo–deoxyuridine (BrdU) into the vitreous chamber and intraperitoneal space, and performed immunohistochemistry staining for BrdU and cell specific markers. To test whether exogenous growth factors stimulate proliferating cells, we injected growth factors into the vitreous chamber after NMDA treatment. We next misexpressed bHLH and homeobox genes in NMDA–treated retinas using a retroviral expression system. Results:Muller glia of adult mammalian retina proliferated in response to acute damage. These cells acquired a progenitor–like phenotype, and some of them migrated to the ONL. Although most remained undifferentiated or differentiated to Muller glia, a few of these cells expressed bipolar specific or rod photoreceptor specific markers. Retinoic acid treatment increased bipolar cell genesis. Misexpression of Math3 or NeuroD along with Pax6 promoted differentiation to amacrine cells. Furthermore, co–expression of Crx and NeuroD promoted rod genesis. Conclusions:These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Muller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in human retinal degenerative diseases.

Keywords: regeneration • retina • Muller cells 
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