Abstract
Purpose :
To characterize the retinal morphology and visual function of sphingosine-1-phosphate receptor 3 knockout (S1PR3KO) mice.
Methods :
Spingosine-1-phosphate receptor 3 (S1PR3KO) and C57BL/6J mice of both genders, ages 1-10 months, Rpbms, Iba-1, CRALBP, GFP, RPE65, Neuroligin2, Synaptophysin, PSD95 and other antibodies. Pattern and flash electroretinogram (PERG and FERG), embedding, fixation and confocal microscopy. All results were subjected to statistical analysis. The retina and optic nerve samples were also subjected to biochemical and mass spectrometric analyses following published protocols.
Results :
We found significant functional PERG differences in S1PR3KO mice between 7 and 8 months of age. There was significant reduction in PERG amplitude at 8 months (5±2 µV) of age in S1PR3KO compared to that at 7 months (20±5 µV) of age, whereas FERG remained unaltered [results are mean± standard deviation for n=6 (equal male and female mice)]. Control C57BL/6J mice showed no difference during 7-10 months of age for these assessments. At 7 months of age the average individual PERG amplitude for S1PR3KO is a little (2-6 µV) less than that for C57BL/6J of the same age but average for n=6 mice in each group the difference was not statistically significant. We found largely single retinal ganglion cell (RGC) layer in S1PR3KO mice at all ages; C57BL/6J mice showed a 2-3 RGC layer. For S1PR3KO mice, although hematoxylin-eosin staining showed no difference in gross morphology of the retina, the PSD95 and Neuroligin2 showed a disordered pattern at 8 months of age compared to that at 7 months. C57BL/6J mice showed consistent patterns throughout the assessment period of 7-10 months. All data were subjected to Student’s t-test or two-way ANOVA as appropriate. The PERG amplitude differences were found to be statistically significant.
Conclusions :
S1PR3KO mice shows both morphological and functional electrophysiological changes at 8 months of age compared to that at 7 months of age suggesting dramatic age-related retinal alteration in these mice.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.