September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A novel model of type 1 diabetes shows neuronal, glial and vascular pathology.
Author Affiliations & Notes
  • Erica L Fletcher
    Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
  • Michael Dixon
    Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
  • Samuel Alexander Mills
    Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
  • Joanna Phipps
    Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
  • Kirstan Vessey
    Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
  • Dirk Wedekind
    Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Germany
  • Andrew Ian Jobling
    Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia
  • Footnotes
    Commercial Relationships   Erica Fletcher, None; Michael Dixon, None; Samuel Mills, None; Joanna Phipps, None; Kirstan Vessey, None; Dirk Wedekind, None; Andrew Jobling, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2714. doi:
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      Erica L Fletcher, Michael Dixon, Samuel Alexander Mills, Joanna Phipps, Kirstan Vessey, Dirk Wedekind, Andrew Ian Jobling; A novel model of type 1 diabetes shows neuronal, glial and vascular pathology.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2714.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : There are numerous murine models of diabetic retinopathy (DR) exhibiting functional, neuronal and/or glial pathology. Despite this, these models generally fail to develop a vascular phenotype typical of DR. This work characterises the retinal neuronal, glial and vascular phenotype of a novel model of autoimmune-mediated type 1 diabetes, the LEW1.AR1/Ztm-iddm rat.

Methods : Autoimmune destruction of pancreatic beta cells and subsequent hyperglycaemia occurs in approximately 60% of LEW.1AR1/Ztm-iddm rats. Retinal phenotype was characterised in healthy and diabetic animals at 6 (~4 month diabetic, n=4) and 9 (7 month diabetic, n=4) months of age. Fixed retinae (4% paraformaldehyde) were immunohistochemically stained with specific retinal cellular markers to explore the cone photoreceptor number (peanut agglutinin), Müller cell gliosis (glial fibrillary acidic protein), microglial number (Ionized calcium binding adaptor molecule 1) and vascular pathology (Isolectin B4). Changes in these markers were quantified across the retina.

Results : Hyperglycaemia developed in the majority of LEW.1AR1/Ztm-iddm rats after approximately 2 months (67 ± 2 days, n=26). There was no gross alteration in retinal structure at any age, with outer nuclear layer thickness not changed between diabetic and control animals in central (9 month; 54 ± 4µm versus 53 ± 2 µm, p>0.05) or peripheral (9 month; 43 ± 2µm versus 44 ± 2 µm, p>0.05) retina. By contrast, cone photoreceptor number was decreased across the retina in both the 6 and 9 month diabetic animals (6 month 16 ± 2%; 9 month 10 ± 4%), while Müller cells exhibited increased gliosis at both ages (6 month, 64 ± 8%; 9 month, 49 ± 6%). Analysis of the retinal vasculature in flat mount showed no alteration in the retinal area covered by the arterioles / venules (control, 4.0 ± 0.2; diabetic, 4.3 ± 0.3, p>0.05), however, there was a significant increase in capillary area in the diabetic animals (control, 7.1 ± 0.4; diabetic, 9.2 ± 0.38, p<0.05). Analysis of retinal microglia showed no increase in cell number or in the number of contacts with blood vessels.

Conclusions : The LEW.1AR1/Ztm-iddm rat shows many of the hallmark features of diabetic retinopathy, such as photoreceptor loss and retinal gliosis. Importantly this rat model also shows an increase in capillary area, providing a novel system in which to investigate the vascular changes common to human patients with DR.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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