Miller Sally, Hu Sherry Shu-Jung, Leishman Emma, Morgan Dan, Wager-Miller Jim, Mackie Ken, Bradshaw Heather B, Straiker Alex
Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States.
Department of Psychology, National Cheng Kung University, Tainan, Taiwan.
Invest Ophthalmol Vis Sci. 2017 Jun 1;58(7):2930-2938. doi: 10.1167/iovs.16-21330.
GPR119 is a G protein-coupled receptor that may be the endogenous target for 2-oleoylglycerol (2-OG), a lipid related to the endocannabinoid family of neuromodulators. Interest in GPR119 has centered on its role in regulating insulin secretion; however, the role of GPR119 has not been examined in the eye. The purpose of this study was to explore a potential GPR119-based signaling system in the murine eye.
We used a combination of RT-PCR, immunohistochemistry, lipid measurement, and IOP measurement in a normotensive mouse model, with GPR119 knockout mice as controls.
We detected GPR119 mRNA and protein in the anterior eye of the mouse and cow, with GPR119 mRNA levels elevated in female relative to male mice. GPR119 protein expression is most prominent in structures near the angle, including trabecular meshwork, as well as iris and corneal epithelium. We detected 2-OG in the anterior eye and detected alterations in lipid levels in GPR119 knockout versus wild type and also by sex. Last, we found that 2-OG preferentially reduces IOP in female mice in a normotensive model.
In summary, we offer evidence for a GPR119-based signaling system in the mammalian eye, with receptors, ligands, and function in the form of a reduction in IOP. Notably this reduction in pressure is restricted to female mice.
GPR119是一种G蛋白偶联受体，可能是2-油酰甘油（2-OG）的内源性靶点，2-OG是一种与神经调节剂内源性大麻素家族相关的脂质。对GPR119的研究兴趣主要集中在其在调节胰岛素分泌中的作用；然而，GPR119在眼部的作用尚未得到研究。本研究的目的是探索小鼠眼中潜在的基于GPR119的信号系统。
我们在正常血压小鼠模型中结合使用了逆转录聚合酶链反应（RT-PCR）、免疫组织化学、脂质测量和眼压测量，并以GPR119基因敲除小鼠作为对照。
我们在小鼠和牛的眼前部检测到了GPR119 mRNA和蛋白，雌性小鼠的GPR119 mRNA水平相对于雄性小鼠有所升高。GPR119蛋白表达在房角附近的结构中最为显著，包括小梁网，以及虹膜和角膜上皮。我们在眼前部检测到了2-OG，并检测到GPR119基因敲除小鼠与野生型小鼠以及不同性别的脂质水平变化。最后，我们发现在正常血压模型中，2-OG能优先降低雌性小鼠的眼压。
总之，我们为哺乳动物眼中基于GPR119的信号系统提供了证据，该信号系统具有受体、配体，并以降低眼压的形式发挥功能。值得注意的是，这种眼压降低仅限于雌性小鼠。
