May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Protective Effect of Hydrophobic Dipeptide Leu-Ile Against Retinal Ganglion Cell Death in vivo and in vitro. : Involvement of GDNF Induction in Müller Cells
Author Affiliations & Notes
  • Y. Shinohara
    Bioengineering Institute, Nidek Co., Ltd., Aichi, Japan
  • M. Nakatani
    Bioengineering Institute, Nidek Co., Ltd., Aichi, Japan
  • M. Hosoi
    Bioengineering Institute, Nidek Co., Ltd., Aichi, Japan
  • C. Taki
    Bioengineering Institute, Nidek Co., Ltd., Aichi, Japan
  • K. Ohtsuki
    Bioengineering Institute, Nidek Co., Ltd., Aichi, Japan
  • S. Nishimura
    Bioengineering Institute, Nidek Co., Ltd., Aichi, Japan
  • Footnotes
    Commercial Relationships Y. Shinohara, None; M. Nakatani, None; M. Hosoi, None; C. Taki, None; K. Ohtsuki, None; S. Nishimura, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 646. doi:
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      Y. Shinohara, M. Nakatani, M. Hosoi, C. Taki, K. Ohtsuki, S. Nishimura; Protective Effect of Hydrophobic Dipeptide Leu-Ile Against Retinal Ganglion Cell Death in vivo and in vitro. : Involvement of GDNF Induction in Müller Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):646.

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

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Abstract

Purpose:: We investigated whether Leu-Ile, a hydrophobic dipeptide, promotes retinal ganglion cell (RGC) survival in kainic-acid (KA)-induced retinal damage in vivo and in culture. We also examined the involvement of Müller cells in the neuroprotective effect of Leu-Ile.

Methods:: Leu-Ile or saline was injected into the vitreous body of adult rats 2 days before KA injection. Neuronal damage was evaluated 7 days after KA (5 nmol) injection by counting the retrograde fluorogold-labeled RGC densities in the retina and measuring phosphorylated neurofilament (pNF-H) contents in optic nerve extracts by ELISA. Survival-enhancing effect of Leu-Ile in purified RGC culture was evaluated by counting calcein-AM-stained RGCs after being exposed to Leu-Ile for two days. In the retina of Leu-Ile-treated eyes, immunohistochemistry and western blot analysis were conducted to elucidate localization and expression of glial cell line-derived neurotrophic factor (GDNF). After the Müller cell culture was exposed to Leu-Ile for 24 hours, the levels of GDNF expression in Müller cells were estimated by western blotting.

Results:: In KA-injected eyes, treatment with Leu-Ile (37 nmol) significantly inhibited the death of RGCs in the retina compared with the saline-treated control. Furthermore, the loss of pNF-H contents in the optic nerve was reduced by Leu-Ile treatment compared with the control. In cultured RGCs, treatment with 10 µM of Leu-Ile significantly increased the number of surviving RGCs compared with the control culture. Immunohistochemistry of Leu-Ile-injected eyes showed upregulated expression of GDNF in radial staining throughout the retina (presumably Müller cells). Western blot analysis showed increase in protein expression of GDNF in Leu-Ile-exposed Müller cell culture as well as in the retina of Leu-Ile-injected eye.

Conclusions:: Leu-Ile protected RGCs from death after retinal damage. Additionally, our results suggest that Leu-Ile also have indirect protective effects on RGCs via the induction of GDNF in Müller cells.

Keywords: neuroprotection • ganglion cells • Muller cells 
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