Abstract
Sphingosine 1-phosphate (S1P) signaling regulates numerous biological processes including neurogenesis, inflammation and neovascularization. However, little is known about the role of S1P signaling in the eye. In this study, we characterize two sphingosine kinases (SPHK1 and SPHK2), which phosphorylate sphingosine to S1P, and three S1P receptors (S1PR1, S1PR2 and S1PR3) in mouse and rat eyes. We evaluated sphingosine kinase and S1P receptor gene expression at the mRNA level in various rat tissues and rat retinas exposed to light-damage, whole mouse eyes, specific eye structures, and in developing retinas. Furthermore, we determined the localization of sphingosine kinases and S1P receptors in whole rat eyes by immunohistochemistry. Our results unveiled unique expression profiles for both sphingosine kinases and each receptor in ocular tissues. Furthermore, these kinases and S1P receptors are expressed in mammalian retinal cells and the expression of SPHK1, S1PR2 and S1PR3 increased immediately after light damage, which suggests a function in apoptosis and/or light stress responses in the eye. These findings have numerous implications for understanding the role of S1P signaling in the mechanisms of ocular diseases such as retinal inflammatory and degenerative diseases, neovascular eye diseases, glaucoma and corneal diseases.
Highlights
Sphingolipids play diverse roles in the biology of cells and tissues [1]
We have previously shown that targeting sphingosine 1-phosphate (S1P) receptors with FTY-720, which is marketed as a drug for multiple sclerosis, can delay retinal degeneration in light damage and genetic models [44,45]
To understand the roles of S1P signaling in the eye, we first explored the expression of relevant protein coding transcripts throughout the body
Summary
Sphingolipids play diverse roles in the biology of cells and tissues [1] As structural lipids, they are essential to maintaining membrane fluidity and organizing lipid rafts [2,3]. The various species of sphingolipids are found throughout the cell including in the nucleus, cytoplasm, and in the extracellular space as signaling molecules [3,4,5,6] Bioactive sphingolipids such as sphingosine 1-phosphate (S1P) and ceramide (Cer) are recognized as important mediators of many basic cellular processes including cell migration, survival, contraction, proliferation, gene expression and various cell-cell interactions [1,5,7,8,9,10,11,12,13,14,15]. The scope of the sphingolipid system’s impact on mammalian biology has proven to be impressive due to the complexity of the “sphingolipid rheostat” and the many signaling pathways that sphingolipids are involved in
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
