April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
A study of aged GK rats: is tau the missing link between diabetes and Alzheimer’s Disease?
Author Affiliations & Notes
  • Timothy Wong
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
  • Marianne Phillips
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
  • Doris Chan
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
  • Shereen Nizari
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
  • Damian Cummings
    Neuroscience, Physiology & Pharmacology, University College London, London, United Kingdom
  • M Francesca Cordeiro
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
    Western Eye Hospital, Imperial College Healthcare Trust, London, United Kingdom
  • Footnotes
    Commercial Relationships Timothy Wong, None; Marianne Phillips, None; Doris Chan, None; Shereen Nizari, None; Damian Cummings, None; M Francesca Cordeiro, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1721. doi:
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      Timothy Wong, Marianne Phillips, Doris Chan, Shereen Nizari, Damian Cummings, M Francesca Cordeiro; A study of aged GK rats: is tau the missing link between diabetes and Alzheimer’s Disease?. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1721.

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

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Abstract

Purpose: Recent research has shown that despite their different features, diabetes and Alzheimer’s disease (AD) share similar pathophysiology including abnormal glucose metabolism, insulin resistance and impaired insulin signalling. AD is the most common type of dementia and its pathological hallmarks include extracellular β-amyloid plaques and intracellular neurofibrillary tangles (NFTs). Diabetes is a metabolic condition characterized by insulin deficiency (Type 1), insulin resistance and defective insulin signalling (Type 2). Patients with Type 2 diabetes (T2DM) have an approximately 60% increased risk of developing AD. Goto Kakizaki (GK) rats are spontaneously diabetic and are considered a model for T2DM in humans. As the brain and retina share a common embryological origin, we have hypothesised that AD pathology in the brains of AD transgenic mice also occurs in the retina. Here, we investigate whether tau pathology and neurofilamentopathy are present in the retinas of aged GK rats.

Methods: The eyes from 3-, 12- and 18-month old spontaneously diabetic GK rats (n=4 for each age group) and age-matched controls (n=3 for 3-month old; n=4 for 12- and 18-month old) were obtained and embedded in paraffin blocks. Sections from these blocks were stained with antibodies for tau, hyperphosphorylated tau (p-tau) and NF-heavy (NFH). Immunohistochemistry images were visualized and obtained. These images were graded for distribution and fluorescence of the antibodies by three independent observers without knowledge of diabetic or control status.

Results: Analysis showed an age-dependent increase of p-tau (p<0.001) and NFH (p<0.001) in the diabetic retina, but not the control retina. Increased levels of p-tau (p<0.01) and NFH (p<0.001) were found in the diabetic retina as compared to the age-matched control retina. No change of colocalization of p-tau and NFH was found in the control or diabetic retina over time.

Conclusions: Recent evidence has suggested that neurodegeneration is an early phenomenon in DM. This study demonstrated an increase in tau-associated neurodegeneration in the diabetic retina over time and as compared to the control retina. As far as we are aware, this is the first study demonstrating AD tau pathology in the retinas of aged diabetic GK rats.

Keywords: 695 retinal degenerations: cell biology • 499 diabetic retinopathy • 498 diabetes  
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