S1PR1 and snowflake vitreoretinal degeneration: These animal and human data suggest that chronic hypoxic hypoperfusion triggers disruption of S1P-S1PR1 signalling, leading to endothelial injury, BBB dysfunction in SVD, and the potential of the S1P-S1PR1 signalling pathway as a protector of vascular function to prevent BBB leakage and the progressive development of SVD.