A GPR119 Signaling System in the Murine Eye Regulates Intraocular Pressure in a Sex-Dependent Manner

• Published in: Investigative ophthalmology & visual science 2017-06, Vol.58 (7), p.2930-2938
• Main Authors: Miller, Sally, Hu, Sherry Shu-Jung, Leishman, Emma, Morgan, Dan, Wager-Miller, Jim, Mackie, Ken, Bradshaw, Heather B, Straiker, Alex
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Female; Gene Expression Regulation; Glaucoma; Glaucoma - genetics; Glaucoma - metabolism; Glaucoma - physiopathology; Immunohistochemistry; Intraocular Pressure - physiology; Male; Mice; Mice, Knockout; Real-Time Polymerase Chain Reaction; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; RNA, Messenger - genetics; Sex Factors; Signal Transduction
• ISSN: 1552-5783; 0146-0404; 1552-5783
• 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.