The Role of Sphingosine-1-Phosphate Receptor 2 in Mouse Retina Light Responses.

The bioactive sphingolipid sphingosine-1-phosphate (S1P) acts as a ligand for a family of G protein-coupled S1P receptors (S1PR1-5) to participate in a variety of signaling pathways. However, their specific roles in the neural retina remain unclear. We previously showed that S1P receptor subtype 2 (S1PR2) is expressed in murine retinas, primarily in photoreceptors and bipolar cells, and its expression is altered by retinal stress. This study aims to elucidate the role of S1PR2 in the mouse retina. We examined light responses by electroretinography (ERG), structural differences by optical coherence tomography (OCT), and protein levels by immunohistochemistry (IHC) in wild-type (WT) and S1PR2 knockout (KO) mice at various ages between 3 and 6 months. We found that a- and b-wave responses significantly increased at flash intensities between 400~2000 and 4~2000 cd.s/m2, respectively, in S1PR2 KO mice relative to those of WT controls at baseline. S1PR2 KO mice also exhibited significantly increased retinal nerve fiber layer (RNFL) and outer plexiform layer (OPL) thickness by OCT relative to the WT. Finally, in S1PR2 KO mice, we observed differential labeling of synaptic markers by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). These results suggest a specific involvement of S1PR2 in the structure and synaptic organization of the retina and a potential role in light-mediated functioning of the retina.

The Effects of Aging on Rod Bipolar Cell Ribbon Synapses.

The global health concern posed by age-related visual impairment highlights the need for further research focused on the visual changes that occur during the process of aging. To date, multiple sensory alterations related to aging have been identified, including morphological and functional changes in inner hair cochlear cells, photoreceptors, and retinal ganglion cells. While some age-related morphological changes are known to occur in rod bipolar cells in the retina, their effects on these cells and on their connection to other cells via ribbon synapses remain elusive. To investigate the effects of aging on rod bipolar cells and their ribbon synapses, we compared synaptic calcium currents, calcium dynamics, and exocytosis in zebrafish (Danio rerio) that were middle-aged (MA,18 months) or old-aged (OA, 36 months). The bipolar cell terminal in OA zebrafish exhibited a two-fold reduction in number of synaptic ribbons, an increased ribbon length, and a decrease in local Ca2+ signals at the tested ribbon location, with little change in the overall magnitude of the calcium current or exocytosis in response to brief pulses. Staining of the synaptic ribbons with antibodies specific for PKCa revealed shortening of the inner nuclear and plexiform layers (INL and IPL). These findings shed light on age-related changes in the retina that are related to synaptic ribbons and calcium signals.

The role of sphingosine-1-phosphate receptor 2 in mouse retina light responses.

The bioactive sphingolipid sphingosine-1-phosphate (S1P) acts as a ligand for a family of G protein-coupled S1P receptors (S1PR1-5) to participate in a variety of signaling pathways. However, their specific roles in the neural retina remain unclear. We previously showed that S1P receptor subtype 2 (S1PR2) is expressed in murine retinas, primarily in photoreceptors and bipolar cells, and its expression is altered by retinal stress. This study aims to elucidate the role of S1PR2 in the mouse retina. We examined light responses by electroretinography (ERG), structural differences by optical coherence tomography (OCT), and protein levels by immunohistochemistry (IHC) in wild-type (WT) and S1PR2 knockout (KO) mice at various ages between 3 and 6 months. We found that a- and b-wave responses significantly increased at flash intensities between 400∼2000 and 4∼2,000 cd.s/m 2 respectively, in S1PR2 KO mice relative to those of WT controls at baseline. S1PR2 KO mice also exhibited significantly increased retinal nerve fiber layer (RNFL) and outer plexiform layer (OPL) thickness by OCT relative to the WT. Finally, in S1PR2 KO mice, we observed differential labeling of synaptic markers by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). These results suggest a specific involvement of S1PR2 in the structure and synaptic organization of the retina and a potential role in light-mediated functioning of the retina.