Abstract
Purpose :
Sphingolipids are essential components of every cell membrane. Recently, a signaling role of bioactive sphingolipids such as ceramide and sphingosine 1-phosphate (S1P) has been established. Ceramide induces apoptosis while S1P plays an anti-apoptotic role. S1P signals through G-protein coupled receptors. In mammalian cells, S1P is produced from sphingosine by two kinases, sphingosine kinase 1 (SPHK1) and 2 (SPHK2). There is little or no information on the role of SPHKs in mammalian retina. Here we characterized the retina of Sphk1 knock-out mice structurally and functionally to determine the role of this kinase in mammalian retinal development and function.
Methods :
We reared albino Sphk1 knock-out mice in dim (5-10 lux) and ambient room light (100-150 lux) for 6 months. We studied rod and cone photoreceptor function by electroretinography (ERG) and structure of all the layers of the retina by OCT and histology. Ultrastructural analysis was done by transmission electron microscopy. We further subjected the dim reared mice to light damage at 500 lux for 10 h at night and analyzed their retina by histology, ERG and OCT after 7 days. Littermate wild type mice reared in similar conditions served as controls for each respective experiment.
Results :
We detected no difference in retinal function in albino Sphk1 knock-out mice reared in dim light for 6 months. However, mice reared in ambient light showed reduction in rod function at 3 months of age and both rod and cone function at 6 months. Our initial ultrastructural analysis shows an abnormality in the structure of outer limiting membrane and inner segments of the retinal of knock-out mice. We also detected RPE vacuoles that are higher in number and bigger in size in the Sphk1 knock-out mice. The albino Sphk1 knock-out mice appear to be slightly resistant to light damage compared to their wildtype littermate.
Conclusions :
We previously showed Ceramide and S1P play a critical role in photoreceptor cell death and retinal degeneration. This first characterization of the retina of Sphk1 knock-out mice suggest that there is a role of S1P and its receptors in the development and organization of mammalian retina and function of the retina in normal and in stress conditions.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.