Changes in Interleukin 18 in the Retinas of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes

Abstract

Recent findings have implicated the involvement of interferon-γ (IFN-γ), a part of the Th1 cytokine response, in the retinal inflammation of diabetic patients. In the present study, we investigate whether hyperglycemia relates to the expression of interleukin 18 (IL-18), and leads to the production of IFN-γ in the retinas of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Plasma blood glucose, triglyceride and cholesterol levels in 60-week-old OLETF rats, in which the development of diabetes mellitus was observed, were significantly higher than in 60-week-old Long-Evans Tokushima Otsuka (LETO) rats used as normal controls. The expression levels of genes that cause IL-18 activation (IL-18, IL-18 receptor and caspase-1) in OLETF rats were increased at 60 weeks of age, and the levels of IL-18 and IFN-γ in 60-week-old OLETF rat retinas were also higher than in 60-week-old LETO rats. Furthermore, IFN-γ levels increased with increasing IL-18 levels in the retinas of OLETF rats, and a close relationship was observed between the levels of IL-18 and HbA1c. The rapid increase in plasma glucose levels following the oral administration of glucose solution (3.0 g/kg) did not affect the IL-18 and IFN-γ levels in the retinas of LETO rats, whereas the levels in the retinas of OLETF rats increased significantly. In conclusion, the expression of IL-18 is increased in the retinas of OLETF rats, and chronic hyperglycemia may accelerate the release of IL-18 and IFN-γ from inflammatory cells in retinal blood vessel. It is possible that IFN-γ production via IL-18 in the retinas of 60-week-old OLETF rats is caused by hyperglycemia, and plays a role in the inflammation of the OLETF rat retinas.