Gene/Protein
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Pivot Concepts:
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Target Concepts:
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Query: UMLS:C0851184 (
thinning
)
11,252
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sphingosine 1-phosphate
(
S1P
) is a potent lipid mediator that modulates inflammation and angiogenesis. In this study, we investigated the possible involvement of
S1P
in the pathology of light-induced retinal degeneration in vivo and in vitro. The intracellular
S1P
and sphingosine kinase (SphK) activity in a photoreceptor cell line (661W cells) was significantly increased by exposure to light. The enhancement of SphK1 expression was dependent on illumination, and all-trans-retinal significantly promoted SphK1 expression.
S1P
treatment reduced protein kinase B (Akt) phosphorylation and increased the protein expression of cleaved caspase-3, and induced photoreceptor cell apoptosis. In vivo, light exposure enhanced the expression of SphK1 in the outer segments of photoreceptors. Intravitreal injection of a SphK inhibitor significantly suppressed the
thinning
of the outer nuclear layer and ameliorated the attenuation of the amplitudes of a-waves and b-waves of electroretinograms during light-induced retinal degeneration. These findings imply that light exposure induces the synthesis of
S1P
in photoreceptors by upregulating SphK1, which is facilitated by all-trans-retinal, causing retinal degeneration. Inhibition of this enhancement may be a therapeutic target of outer retinal degeneration, including age-related macular degeneration.
...
PMID:Light Stress-Induced Increase of Sphingosine 1-Phosphate in Photoreceptors and Its Relevance to Retinal Degeneration. 3135 84
