Background: The etiopathogenesis of vernal keratoconjunctivitis (VKC),
is incompletely understood. Bioactive lipids play a key role in the
allergic disorders and there are no studies exploring it in the ocular
surface allergic disorder such as VKC. This study focused on the
sphingolipid metabolism in VKC and explored the association of ocular
surface sphingolipids with the refractory nature of the disease.
Methods: Active VKC cases and age-matched healthy controls were
recruited as part of a one-year prospective study at our tertiary eye
care centre in South India. Imprint cytology was used to assess gene
expression of enzymes of sphingolipids metabolism in conjunctival cells.
Sphingolipids levels were estimated in the tears by LC-MS/MS analysis.
Systemic levels of Sphingosine-1-phosphate (S1P) and
Ceramide-1-Phosphate and IgE were estimated by ELISA. IgE induced
regulation of S1P receptor gene expression was assessed by western blot
analysis of histone deacetylases in cultured mast cells. Results:
Significantly altered gene expression of the sphingolipids enzymes was
noted in VKC in conjunctival cells. Pooled tears showed significantly
lowered levels of S1P (d17:1), S1P (d17:0) and S1P (d20:1) in VKC.
Additionally, Cer (d18:/17:0) was significantly lowered in R-VKC
compared to NR-VKC. Lowered C1P and raised IgE were observed at serum
level in VKC. Increased S1P receptors and histone deacetylases
expression indicate regulation by histone modification as evaluated in
IgE induced mast cells. Conclusion: Altered sphingolipid metabolism is
associated with VKC pathogenesis and is differential in refractory cases
that showed lower ceramide and specific sphingosines compared to