Ocular surface sphingolipids associate with the refractory nature of vernal keratoconjunctivitis: newer insights in VKC pathogenesis

BackgroundThe etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allergic disorders. This study focused on the sphingolipid metabolism on the ocular surface of VKC and to explore if it has a contributory role in the refractoriness of the disease.MethodsActive VKC cases, (n=87) (classified as mild/moderate and severe/very severe based on the disease symptoms) and age-matched healthy controls (n=60) were recruited as part of a 2-year prospective study at a tertiary eye care centre in South India. Conjunctival imprint cytology was used to assess gene expression of enzymes of sphingolipids metabolism. Sphingolipids were estimated in the tears by LC-MS/MS analysis. In vitro study was done to assess IgE-induced alterations in sphingosine-1-phosphate (S1P) receptor expression and histone modification in cultured mast cells.ResultsSignificantly altered gene expression of the sphingolipids enzymes and S1P receptor (SIP3R) were observed in conjunctival imprint cells of VKC cases. Pooled tears analysis revealed significantly lowered levels of S1P(d17:0), S1P(d20:1) (p