Original Article Absence of clinical correlates of diabetic retinopathy in the Ins2 Akita retina Samuel McLenachan PhD, 1,2 Xiangting Chen BSc Hons, 3 Paul G McMenamin DSc(Med) 3 and Elizabeth P Rakoczy PhD 1,2 1 Centre for Ophthalmology and Visual Science, The University of Western Australia, 2 Department of Molecular Ophthalmology, Lions Eye Institute, Perth, Western Australia, and 3 Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Victoria, Australia ABSTRACT Background: The Ins2 Akita mouse has been reported to display retinal pathology degeneration associated with advanced diabetic retinopathy. In the present study, we monitored retinal changes in these mice to establish if this model displays clinical features asso- ciated with advanced diabetic retinopathy in human patients. Methods: Ins2 Akita mice (n = 55) on a C57Bl/6J back- ground were monitored clinically from 9 to 25 weeks of age using a combination of scanning laser oph- thalmoscopy, fluorescein angiography and optical coherence tomography. After clinical imaging, eyes were processed for immunostaining to examine microglial, astroglial and Muller glial responses to hyperglycaemia. To complement our optical coher- ence tomography imaging, retinal morphology and thicknesses were examined in high-quality semi- thin sections. Results: No retinal thinning or disruption of retinal architecture was observed by optical coherence tomography or resin histology in Ins2 Akita mice up to 6 months of age. In addition, no vascular changes were detected by fluorescein angiography or by scanning laser ophthalmoscopy. With the exception of microglial activation, reduced glial fibrillary acid protein expression in astrocytes and an increase in glial fibrillary acid protein expression by Muller cells, no other changes were observed in the Ins2 Akita retina. Conclusions: Our results indicate that the classical clinical correlates of human diabetic retinopathy are absent in Ins2 Akita mice up to 6 months of age sug- gesting that either the histopathological processes underlying the development of diabetic retinopathy in this model require longer than 5 months of hyper- glycaemia to result in disruption of retinal architec- ture or that advanced diabetic retinopathy is not a feature of the Ins2 Akita diabetic mouse. Key words: diabetes, Ins2 Akita , retinopathy. INTRODUCTION Diabetic retinopathy (DR) is the third most common cause of blindness in developed countries and is the leading cause of blindness in working age adults. 1 Australian and US-based studies indicate that between 50% and 97% of patients with type 1 dia- betes mellitus have signs of DR by 15–20 years postdiagnosis. 2 DR is also a complication of type 2 (late onset) diabetes, with 40% of patients having some evidence of retinopathy and 8% with vision- threatening disease. 3 Despite this, the treatment for DR has remained largely unchanged since the advent of laser therapy, which is targeted at the late-stage vasoproliferative phase of the disease. Treatments targeting the early preproliferative stage of DR are hampered by our poor understanding of  Correspondence: Professor Elizabeth Rakoczy, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia. Email: elizabeth.rakoczy@uwa.edu.au Received 28 August 2012; accepted 25 December 2012. Competing/conflicts of interest: No stated conflict of interest. Funding sources: NHMRC Australia Grant no. 634469. Clinical and Experimental Ophthalmology 2013; 41: 582–592 doi: 10.1111/ceo.12084 © 2013 The Authors Clinical and Experimental Ophthalmology © 2013 Royal Australian and New Zealand College of Ophthalmologists