Kristina J H Kleinwort1, Barbara Amann1, Stefanie M Hauck2,3, Sieglinde Hirmer1, Andreas Blutke4, Simone Renner3,5, Patrizia B Uhl1, Karina Lutterberg1, Walter Sekundo6, Eckhard Wolf3,5, Cornelia A Deeg7. 1. Institute of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany. 2. Research Unit Protein Science, Helmholtz Zentrum München, German Research Centre for Environmental Health GmbH, Munich, Germany. 3. German Centre for Diabetes Research (DZD), Neuherberg, Germany. 4. Institute of Veterinary Pathology, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany. 5. Molecular Animal Breeding and Biotechnology, Gene Centre, LMU Munich, Munich, Germany. 6. Department of Ophthalmology, Philipps University of Marburg, Marburg, Germany. 7. Experimental Ophthalmology, Philipps University of Marburg, Baldingerstrasse, D-35033, Marburg, Germany. Cornelia.Deeg@uni-marburg.de.
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 INS C94Y 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 INS C94Y pigs exposed to hyperglycaemia for more than 2 years, representing a chronic diabetic condition. METHODS: Eyes from six INS C94Ypigs 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: INS C94Ypigs 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 INS C94Ypig is an interesting model for studying the pathophysiology of diabetic retinopathy and for testing novel therapeutic strategies.
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 INS C94Y 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 INS C94Ypigs exposed to hyperglycaemia for more than 2 years, representing a chronic diabetic condition. METHODS: Eyes from six INS C94Ypigs 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 humandiabetic retinopathy. RESULTS: INS C94Ypigs 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 INS C94Ypig is an interesting model for studying the pathophysiology of diabetic retinopathy and for testing novel therapeutic strategies.
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