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).