March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Manifestation Of Neuropathy In The Corneal Nerve Plexus Of Diabetic Nod Mice
Author Affiliations & Notes
  • Simone Baltrusch
    Institute of Medical Biochemistry,
    University of Rostock, Rostock, Germany
  • Maria Reichard
    Department of Ophthalmology,
    University of Rostock, Rostock, Germany
  • Heike Weiss
    Institute of Medical Biochemistry,
    University of Rostock, Rostock, Germany
  • Markus Tiedge
    Institute of Medical Biochemistry,
    University of Rostock, Rostock, Germany
  • Rudolf Guthoff
    Department of Ophthalmology,
    University of Rostock, Rostock, Germany
  • Oliver Stachs
    Department of Ophthalmology,
    University of Rostock, Rostock, Germany
  • Footnotes
    Commercial Relationships  Simone Baltrusch, None; Maria Reichard, None; Heike Weiss, None; Markus Tiedge, None; Rudolf Guthoff, None; Oliver Stachs, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1814. doi:
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      Simone Baltrusch, Maria Reichard, Heike Weiss, Markus Tiedge, Rudolf Guthoff, Oliver Stachs; Manifestation Of Neuropathy In The Corneal Nerve Plexus Of Diabetic Nod Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1814.

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

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Abstract

Purpose: : Patients with type 1 diabetes mellitus have a high risk to develop small fibre neuropathy. In-vivo confocal laser scanning microscopy facilitates the examination of alterations in the corneal subepithelial nerve plexus. The NOD mouse is an established model of type 1 diabetes mellitus. The aim of this study was to investigate the corneal nerve structure in diabetic and healthy NOD mice by confocal laser scanning microscopy together with a metabolic characterization of the animals over time.

Methods: : NOD mice were characterized by measuring auto-antibodies against insulin, blood glucose, HbA1c values, and advanced glycation end products. For confocal laser scanning microscopy the animals were anesthetized. The eye was moistened with a carbomer gel and the cornea was visualized by confocal laser scanning microscopy (HRTII + RCM, Heidelberg Engineering). Thereafter images were analysed using AutoQuantX Software (Media Cybernetics).

Results: : NOD mice with a high level of auto-antibodies against insulin at the age of 20 weeks were classified as diabetic. These animals had with 24 mmol/l and 10.5 % a significant higher blood glucose level and HbA1c value, respectively in comparison to healthy NOD mice (5 mmol/l and 4%). Five healthy and diabetic mice each were examined by corneal confocal laser scanning microscopy every three weeks. A progressive reduction in the homogeneous linear texture of the nerves and an increase in tortuosity were observed in diabetic NOD mice. Quantification of the total number of nerves per image frame revealed a significant reduction in sub-basal nerves in diabetic NOD mice compared to their healthy littermates. In simultaneous performed measurements a significant increase in advanced glycation end products was determined in diabetic NOD mice. Deconvolution of a z-layer image sequence revealed a beaded structure of nerve bundles in healthy mice in a comparable manner as previously described in humans.

Conclusions: : Using in-vivo confocal laser scanning microscopy, we could demonstrate for the first time a reduction of mouse corneal nerves in diabetic NOD mice in comparison to healthy NOD mice. It will be the challenge of further studies to elucidate the nexus between the increase of advanced glycation end products and the alterations in the corneal nerve plexus.

Keywords: diabetes • cornea: basic science • imaging/image analysis: clinical 
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