Kleinwort Kristina J H, Amann Barbara, Hauck Stefanie M, Hirmer Sieglinde, Blutke Andreas, Renner Simone, Uhl Patrizia B, Lutterberg Karina, Sekundo Walter, Wolf Eckhard, Deeg Cornelia A
Institute of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.
Research Unit Protein Science, Helmholtz Zentrum München, German Research Centre for Environmental Health GmbH, Munich, Germany.
Diabetologia. 2017 Aug;60(8):1541-1549. doi: 10.1007/s00125-017-4290-7. Epub 2017 May 8.
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 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 pigs exposed to hyperglycaemia for more than 2 years, representing a chronic diabetic condition.
Eyes from six INS pigs 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.
INS pigs 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 pig is an interesting model for studying the pathophysiology of diabetic retinopathy and for testing novel therapeutic strategies.
目的/假设：糖尿病视网膜病变是糖尿病的一种严重并发症，常导致失明。由于糖尿病视网膜病变的病理生理学尚未完全了解，且需要测试新的治疗干预措施，因此需要可靠的动物模型来模拟糖尿病视网膜病变的所有并发症。猪眼与人眼在重要的解剖学和生理学方面具有相似性。先前的研究表明，胰岛素转基因猪会出现稳定的糖尿病表型和眼部病变，如白内障。本研究的目的是对暴露于高血糖环境超过2年的胰岛素转基因猪的视网膜病理变化进行深入分析，这代表一种慢性糖尿病状态。
通过组织学和免疫组织化学分析6只胰岛素转基因猪和6只年龄匹配的对照同窝仔猪的眼睛。对于视网膜（各层）厚度的组织学分析，切片用苏木精-伊红（H&E）或马洛里三色染色法染色。为了比较蛋白质表达模式和血管走向，在免疫组织化学中用不同抗体对切片进行染色。将观察到的病变与人类糖尿病视网膜病变中报道的病理学进行比较。
胰岛素转基因猪出现了几种与人类相似的糖尿病视网膜病变迹象，如视网膜内微血管异常、增殖性糖尿病视网膜病变症状以及在富含视锥细胞的区域（如人类黄斑区）出现视网膜中央水肿。
结论/解读：胰岛素转基因猪是研究糖尿病视网膜病变病理生理学和测试新治疗策略的一个有趣模型。
