School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Osaka, Japan.
Curr Eye Res. 2011 Jun;36(6):497-506. doi: 10.3109/02713683.2010.549602.
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.
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.
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.
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.
成熟的白细胞介素 18（IL-18）可导致干扰素-γ、核因子 κB 和诱导型一氧化氮合酶的产生，我们之前的研究报道遗传性白内障模型大鼠晶状体中 IL-18 的增强与晶状体混浊有关。在这项研究中，我们研究了 Otsuka Long-Evans Tokushima Fatty（OLETF）大鼠（2 型糖尿病模型）晶状体中 IL-18 的表达是否与晶状体混浊有关。
本研究使用 60 周龄雄性 Long-Evans Tokushima Otsuka（LETO）和 OLETF 大鼠。采用实时定量 RT-PCR 法测定 IL-18 mRNA 的表达，采用 ELISA 法测定 IL-18 和干扰素-γ水平。使用 EAS-1000 监测晶状体的透明度，并通过与 EAS-1000 相连的图像分析软件进行分析。
OLETF 大鼠的血浆葡萄糖、甘油三酯和胆固醇水平明显高于 LETO 大鼠作为正常对照，且观察到糖尿病的发生。在 60 周龄时，导致 IL-18 激活的基因表达水平（IL-18、IL-18 受体和半胱天冬酶-1）升高，60 周龄 OLETF 大鼠晶状体中的 IL-18 和干扰素-γ水平也高于 60 周龄 LETO 大鼠。此外，OLETF 大鼠晶状体中干扰素-γ水平随 IL-18 水平的升高而升高，IL-18 水平与混浊度密切相关。
OLETF 大鼠晶状体中 IL-18 的表达增加。OLETF 大鼠晶状体中激活的 IL-18 可能与晶状体上皮细胞凋亡和晶状体混浊有关。
