May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Characterization of Normal Tension Glaucoma Mouse Over Expressing Mutant OPTN (E50K)
M. Akahori; M. Minami; M. Obazawa; S. Tomarev; N. Nakaya; Y. Miyake; T. Iwata
Author Affiliations & Notes
  • M. Akahori
    National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro–ku, Tokyo, Japan
  • M. Minami
    National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro–ku, Tokyo, Japan
  • M. Obazawa
    National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro–ku, Tokyo, Japan
  • S. Tomarev
    National Eye Institute, National Institutes of Health, Bethesda, MD
  • N. Nakaya
    National Eye Institute, National Institutes of Health, Bethesda, MD
  • Y. Miyake
    National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro–ku, Tokyo, Japan
  • T. Iwata
    National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Meguro–ku, Tokyo, Japan
  • Footnotes
    Commercial Relationships  M. Akahori, None; M. Minami, None; M. Obazawa, None; S. Tomarev, None; N. Nakaya, None; Y. Miyake, None; T. Iwata, None.
  • Footnotes
    Support  Ministry of Education, Culture, Sports, Science and Technology of Japan
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 206. doi:
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      M. Akahori, M. Minami, M. Obazawa, S. Tomarev, N. Nakaya, Y. Miyake, T. Iwata; Characterization of Normal Tension Glaucoma Mouse Over Expressing Mutant OPTN (E50K) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):206.

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Abstract

Purpose: : Recently optineurin (OPTN) was reported as responsible for primary open–angle glaucoma and normal tension glaucoma. This protein was previously characterized to interact with several proteins including small GTP–binding protein Rab8. We had previously reported that one of the mutations in OPTN (E50K) inhibited an interaction with Rab8 protein. To characterize the mutant OPTN (E50K) in relation with Rab8 interaction in vivo, transgenic mouse over expressing mutant OPTN (E50K) was developed.

Methods: : Mouse OPTN was amplified by RT–PCR from C57BL/6 brain total RNA and E50K mutation and deletion of exon 5 were introduced by mutagenesis kit (Stratagene). All cDNA were inserted into transgenic construction vector (pBroad2). Transgenic mouse over expressing mutant OPTN (E50K) and mutant OPTN (deletion exon 5) were developed by YS Institute Inc. (Japan). All transgenic mice were examined by PCR method using genomic DNA extracted from mouse tail. Intraocular pressure was measured by Tonometer (Tonolab) and Optic fiber sensor (FISO technologies). Photograph of optic nerve head was observed by slit lamp with digital camera (Topcon). Histological characterization by HE staining and immunohistochemistry were performed. Apoptosis of retinal ganglion cells were detected by TUNEL kit (Roche).

Results: : Transgenic mouse over expressing OPTN (deletion exon 5) resulted as lethal expression. There was no difference in intraocular pressure between mutant OPTN (E50K) expressing mice and non–transgenic mice. Optic nerve in the surroundings of optic nerve head has decreased and retinal ganglion cells induced apoptosis were observed in mutant OPTN (E50K) expressing mouse.

Conclusions: : Transgenic mouse over expressing wild type, E50K, and Exon 5 deleted OPTN was developed and characterized. Significant effect in retinal ganglion cells of E50K transgenic mouse was observed. This is the first POAG animal model developed by transgenic technology. Abnormality and OPTN–Rab8 interaction in vivo is under investigation.

Keywords: ganglion cells • apoptosis/cell death • optic disc 
© 2006, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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