To the Editor,
Vernal keratoconjunctivitis (VKC) is a chronic bilateral allergic inflammation of the ocular surface, seasonal or perennial affecting children in their first decade of life presenting with varying grades of severity. A small subset borders on refractory disease not amenable to interventions(1). Allergic response in terms of bioactive lipids is underexplored in ocular surface disorders and this study focused on sphingolipids. Ceramide and sphingosine are inter-convertible components of the “sphingolipid rheostat” that regulate immune response. The phosphorylated forms, ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) regulated by the various kinases, phosphatases, hydrolases and lyases act as bioactives. They accumulate in cell membrane and compartmentalize intracellularly to play a major role in immune cell trafficking, inflammation, barrier cell integrity and cell survival(2–4).
A prospective observational study was conducted at a tertiary eye care hospital in South India in 87 cases of VKC (74 M/13 F; Mean age - 12.5 ± 5.3 years) and 60 age matched healthy controls (37M/23F; Mean age -13.7±5.2 years), as approved by the Institutional review board. The study was conducted in strict adherence to the tenets of Declaration of Helsinki after written informed consent from all study participants.
Based on Bonini’s classification(1), VKC patients with grade 1 and 2 were considered non-refractory (NR-VKC) and those with grade 3 and 4 as refractory (R-VKC).
Gene expression of enzymes of sphingolipid metabolism evaluated in the conjunctival cells of VKC cases obtained by imprint cytology(5) showed a significant increase compared to the control, namely in Alkaline ceramidase (ACER) (p<0.05), Sphingosine kinase (SPHK1) (p<0.001, 5 fold increase); Sphingosine-1-phosphate lyase (SGPL) (p<0.001, 20 fold increase); UDP- Glucose ceramide glucosyltransferase (UGCG)(p<0.05), while acid sphingomyelinase (ASMA) was significantly reduced (p<0.01), indicating altered sphingolipid metabolism in VKC with potential accumulation of S1P over that of C1P (Fig 1A ). Concomitantly, S1P receptor, S1PR3 in the conjunctival imprint cells was significantly upregulated indicating cellular accumulation of S1P. While, Bcl2/Bax ratio was down-regulated, vimentin was significantly upregulated in VKC cases compared to control indicating a profibrotic and reduced apoptotic milieu (Fig 1 B, C). An altered sphingolipid metabolism was observed also at systemic level in the VKC cases, wherein there was significant lowering of C1P and an increase in S1P along with raised IgE in serum as per ELISA (Fig 1D).