Diabetologia

, Volume 60, Issue 8, pp 1541–1549

Retinopathy with central oedema in an INSC94Y transgenic pig model of long-term diabetes

  • Kristina J. H. Kleinwort
  • Barbara Amann
  • Stefanie M. Hauck
  • Sieglinde Hirmer
  • Andreas Blutke
  • Simone Renner
  • Patrizia B. Uhl
  • Karina Lutterberg
  • Walter Sekundo
  • Eckhard Wolf
  • Cornelia A. Deeg
Article

Abstract

Aims/hypothesis

Diabetic retinopathy is a severe complication of diabetes mellitus that often leads to blindness. Because the pathophysiology of diabetic retinopathy is not fully understood and novel therapeutic interventions require testing, there is a need for reliable animal models that mimic all the complications of diabetic retinopathy. Pig eyes share important anatomical and physiological similarities with human eyes. Previous studies have demonstrated that INSC94Y transgenic pigs develop a stable diabetic phenotype and ocular alterations such as cataracts. The aim of this study was to conduct an in-depth analysis of pathological changes in retinas from INSC94Y pigs exposed to hyperglycaemia for more than 2 years, representing a chronic diabetic condition.

Methods

Eyes from six INSC94Ypigs and six age-matched control littermates were analysed via histology and immunohistochemistry. For histological analyses of retinal (layer) thickness, sections were stained with H&E or Mallory’s trichrome. For comparison of protein expression patterns and vessel courses, sections were stained with different antibodies in immunohistochemistry. Observed lesions were compared with reported pathologies in human diabetic retinopathy.

Results

INSC94Ypigs developed several signs of diabetic retinopathy similar to those seen in humans, such as intraretinal microvascular abnormalities, symptoms of proliferative diabetic retinopathy and central retinal oedema in a region that is cone rich, like the human macula.

Conclusions/interpretation

The INSC94Ypig is an interesting model for studying the pathophysiology of diabetic retinopathy and for testing novel therapeutic strategies.

Keywords

Animal model Cataract Colour vision Diabetes Eye disease Macular oedema Pathophysiologic processes Retinopathy Vascular complications 

Abbreviations

AQP

Aquaporin

DBA

Dolichos biflorus agglutinin

GS

Glutamine synthetase

LEL

Lycopersicon esculentum lectin

NEFH

Neurofilament heavy chain

SMA

Smooth muscle actin

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Kristina J. H. Kleinwort
    • 1
  • Barbara Amann
    • 1
  • Stefanie M. Hauck
    • 2
    • 3
  • Sieglinde Hirmer
    • 1
  • Andreas Blutke
    • 4
  • Simone Renner
    • 3
    • 5
  • Patrizia B. Uhl
    • 1
  • Karina Lutterberg
    • 1
  • Walter Sekundo
    • 6
  • Eckhard Wolf
    • 3
    • 5
  • Cornelia A. Deeg
    • 7
  1. 1.Institute of Animal Physiology, Department of Veterinary SciencesLMU MunichMunichGermany
  2. 2.Research Unit Protein Science, Helmholtz Zentrum MünchenGerman Research Centre for Environmental Health GmbHMunichGermany
  3. 3.German Centre for Diabetes Research (DZD)NeuherbergGermany
  4. 4.Institute of Veterinary Pathology, Centre for Clinical Veterinary MedicineLMU MunichMunichGermany
  5. 5.Molecular Animal Breeding and Biotechnology, Gene CentreLMU MunichMunichGermany
  6. 6.Department of OphthalmologyPhilipps University of MarburgMarburgGermany
  7. 7.Experimental OphthalmologyPhilipps University of MarburgMarburgGermany

Personalised recommendations