Retinopathy with central oedema in an INS C94Y transgenic pig model of long-term diabetes
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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.
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.
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.
The INS C94Ypig is an interesting model for studying the pathophysiology of diabetic retinopathy and for testing novel therapeutic strategies.
KeywordsAnimal model Cataract Colour vision Diabetes Eye disease Macular oedema Pathophysiologic processes Retinopathy Vascular complications
Dolichos biflorus agglutinin
Lycopersicon esculentum lectin
Neurofilament heavy chain
Smooth muscle actin
The authors thank S. Nüske and A. Scholz (Teaching and Experimental Farm, LMU Munich) for providing pig control tissues. We thank R. Degroote (Institute of Animal Physiology, LMU Munich) for critically revising the manuscript and R. Wanke (Institute of Animal Pathology, LMU Munich) for critical discussions.
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
This work was supported by the von Behring-Röntgen Foundation (63-0004); the Foundation for the Support of Science in Ophthalmology Marburg e.V. (to CAD); the Federal Ministry of Education and Research (16EX1024A); and the German Centre for Diabetes Research (DZD) (to EW).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
CAD conceived and designed the experiments. KJHK, BA, SH, SMH, PBU, KL and CAD performed the experiments. KJHK, BA, SH, SMH, PBU, KL, WS, EW and CAD analysed the data. SR, AB and EW developed and characterised the INS C94Ypig model. CAD wrote the manuscript. All authors critically read and provided comments on the manuscript. All authors approved the final version to be published. CAD is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.