Sphingosine 1-phosphate (S1P), a lysophospholipid mediator, is associated with various cellular processes. In this study, we investigated whether S1P is involved in the pathology of light-induced retinal degeneration. Light exposure significantly enhanced the intracellular S1P and sphingosine kinase (SphK) activity in a photoreceptor cell line (661W cell line). Moreover, SphK1 expression increased in an illuminance-dependent manner, and all-trans-retinal significantly promoted SphK1 expression. S1P treatment decreased the phosphorylation of protein kinase B (Akt), increased the expression of cleaved caspase-3, and induced the apoptosis of photoreceptor cells. In vivo, light exposure increased the expression of SphK1 in the outer segment of the retina. An intravitreal injection of an SphK inhibitor significantly decreased the thinning of the outer nuclear layer and suppressed the reduction of the a-wave and b-wave amplitudes of electroretinograms during light-induced retinal degeneration. These findings indicate that light exposure upregulates SphK1 expression in the outer segment of the retina and induces the synthesis of S1P in photoreceptors, which is facilitated by all-trans-retinal, leading to light-induced retinal degeneration. The inhibition of this enhancement may be a therapeutic target for treating outer retinal degeneration, including age-related macular degeneration.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 125: 1013-1022,2021.