May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Nicotinamide Mononucleotide Adenylyltransferase1 (Nmnat1) in TNF--Induced Optic Nerve Degeneration
Author Affiliations & Notes
  • Y. Kitaoka
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • Y. Hayashi
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • H. Fujino
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • Y. Kitaoka
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • F. N. Ross-Cisneros
    Neuro-Ophthalmology, Doheny Eye Institute/USC, Los Angeles, California
  • Y. Munemasa
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
    Ophthalmology, Jules Stein Eye Institute/UCLA, Los Angeles, California
  • S. Ueno
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • A. A. Sadun
    Neuro-Ophthalmology, Doheny Eye Institute/USC, Los Angeles, California
  • T. T. Lam
    Neuro-Ophthalmology, Doheny Eye Institute/USC, Los Angeles, California
  • Footnotes
    Commercial Relationships Y. Kitaoka, None; Y. Hayashi, None; H. Fujino, None; Y. Kitaoka, None; F.N. Ross-Cisneros, None; Y. Munemasa, None; S. Ueno, None; A.A. Sadun, None; T.T. Lam, None.
  • Footnotes
    Support Grants-in-aid for scientific research of Japanese Ministry of Education, Culture, Sports, Science and Technology (No. 18791303); the Imai Memorial Foundation for Glaucoma Research
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2454. doi:https://doi.org/
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      Y. Kitaoka, Y. Hayashi, H. Fujino, Y. Kitaoka, F. N. Ross-Cisneros, Y. Munemasa, S. Ueno, A. A. Sadun, T. T. Lam; Nicotinamide Mononucleotide Adenylyltransferase1 (Nmnat1) in TNF--Induced Optic Nerve Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2454. doi: https://doi.org/.

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

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Abstract

Purpose:: To examine the involvement of nmnat1 in TNF-α-induced optic nerve degeneration and evaluate the effect of nicotinamide adenine dinucleotide (NAD) on axonal loss and retinal ganglion cell (RGC) loss induced by TNF-α.

Methods:: Rats were euthanized at 1 day, 2 weeks, or 2 months after PBS or TNF-α (10 ng) intravitreal injection. NAD was injected intravitreally 24 hr before TNF-α injection. Nmnat1 mRNA in the optic nerve and retina was evaluated by quantitative real-time PCR. Fluorogold retrograde labeling of RGCs was performed 5 days before the intravitreal injection. The effects of NAD on TNF-α-induced optic nerve degeneration were determined by transmission electron microscopy (TEM) as well as axon number counting.

Results:: Real-time PCR showed that the level of nmnat1 mRNA was significantly decreased (to 45.2 % of control) in the optic nerve of TNF-α-treated eyes compared with that of PBS-treated eyes. However, no significant difference in nmnat1 mRNA level was observed in the retina between TNF-α-treated eyes and PBS-treated eyes. TEM study showed that TNF-α caused disorganization of the microtubules with vacuoles and myelin damage 2 weeks after injection. These TEM findings were blocked with pre-treatment of NAD. Moreover, NAD significantly prevented TNF-α-induced axonal loss evaluated by morphometric analysis. Exogenous NAD did not alter the decrease in mRNA of nmnat1 induced by TNF-α. Fluorogold labeling analysis showed that NAD ameliorated RGC loss 2 months after TNF-α injection.

Conclusions:: Axonal nmnat1 decline may be associated with TNF-α induced optic nerve axonal degeneration. Preventing axonal degeneration with NAD may lead to protective effect on delayed loss of RGC bodies.

Keywords: neuro-ophthalmology: optic nerve • neuroprotection • microscopy: electron microscopy 
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