Involvement of interleukin 18 in lens opacification of Otsuka Long-Evans Tokushima Fatty rats, a model of human type 2 diabetes.

PURPOSE

Mature interleukin 18 (IL-18) leads to the production of interferon-γ, nuclear factor kappa B, and inducible nitric oxide synthase, and we previously reported that the enhancement of IL-18 in lens of hereditary cataract model rats was involved in lens opacification. In this study, we investigated whether the expression of IL-18 relates to lens opacification in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus.

METHODS

Male Long-Evans Tokushima Otsuka (LETO) and OLETF rats at 60 weeks of age were used in this study. Expression of IL-18 mRNA was measured by quantitative real-time RT-PCR method, and IL-18 and interferon-γ levels were determined using the ELISA method. The transparency of the lenses was monitored using an EAS-1000, and analyzed by image analysis software connected to the EAS-1000.

RESULTS

The plasma levels of glucose, triglycerides and cholesterol in the OLETF rats were significantly higher than in LETO rats as normal controls, and the development of diabetes mellitus was observed. The gene expression levels causing IL-18 activation (IL-18, IL-18 receptor, and caspase-1) are increased at 60 weeks of age, and the levels of IL-18 and interferon-γ in 60-week-old OLETF rat lenses were also higher than those in the 60-week-old LETO rat. Furthermore, the interferon-γ levels increased with increasing IL-18 levels in the lenses of OLETF rat, and a close relationship was observed between the levels of IL-18 and opacity.

CONCLUSION

The expression of IL-18 was increased in the lenses of OLETF rat. It is possible that activated IL-18 in the lenses of OLETF rat may be related to the lens epithelial cell apotosis and lens opacification.