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Akifumi Yamamoto, Osamu Sakai, Hideki Tokushige; The characteristics of diabetic retinopathy in ZDF type-2 diabetes rats. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5368. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The streptozotocin (STZ) -induced diabetic rodent model mimics type-1 diabetes, and this model is the most common model which has been used for diabetic retinopathy (DR) research. The majority of human diabetic patients is type-2 diabetes, therefore the STZ-induced diabetic model is not suitable for research on the type-2 diabetes. Zucker diabetic fatty (ZDF) rats are well known as a model of type-2 diabetes induced nephropathy and neuropathy, however the development of DR in ZDF rats are still unknown. The purpose of this study was to investigate the expressions of protein and gene associated with progression of DR and retinal changes in ZDF rats in order to clarify the characteristics.
We used 13-21 weeks old ZDF obese rats (fatty rats). Age-matched ZDF lean rats (lean rats) were used as control. The animals were euthanized at 21 weeks old, and the retinas were collected for protein and gene expression change analysis. Vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and -2 (Ang-2) mRNA expressions were examined by qRT-PCR. VEGF protein expression was examined by ELISA. ZO-1 protein expression was examined by western blotting. The retinal vascular permeability was quantified by FITC-albumin extravasations. The retinal thickness was measured using optical coherent tomography (OCT) at 13 and 17 weeks old. Fluorescein angiography (FA) was performed to detect retinal vascular changes and leakage at 13 and 17 weeks old.
The blood glucose level of the fatty rats was higher than that of the lean rats. The retinal VEGF and Ang-2 mRNA expressions were significantly increased in the fatty rats compared with the lean rats, whereas there is no difference between the fatty and lean rats in Ang-1 mRNA expression. Furthermore, the retinal VEGF protein expression showed a tendency to increase in the fatty rats, and the retinal ZO-1 protein expression significantly decreased in the fatty rats compared with the lean rats. However, the clinical signs such as retinal edema, major vascular abnormalities and leakage did not occur in the fatty rats.
Although the clinical signs were not observed, the protein expression profiles of the fatty rats mimic the pathology in type-2 diabetic patients with DR. This model may be useful for the DR research and evaluation of drugs for DR treatment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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