Introduction:
Vernal keratoconjunctivitis (VKC) is a chronic, bilateral allergic
inflammation of the ocular surface, seasonal or perennial affecting
children in the first decade of their life. It can present as limbal,
palpebral or as a mixed disease with varying grades of severity, with a
small subset bordering on refractory disease not amenable to currently
available treatment modalities(1). Being a tropical country, the
incidence is high in India and almost 36% children have the perennial
form of VKC(2).
The exact etiopathogenesis of allergic disorders is still not completely
understood. Pathways involving IgE antibodies or T-cells and
inflammatory cytokines(3,4) are well known. However, the ones involving
bioactive lipid mediators are still being explored. Of the four classes
of immune modulating lipids; platelet activating factor, leukotrienes,
prostanoids and sphingolipids, immense focus has been on the
sphingolipid group in influencing the pathogenesis of allergic disease
as seen in the last decade(5). Sphingolipids (SL) comprise a large
family of bioactive lipids containing a sphingoid base (aliphatic amino
alcohol) as backbone that is acylated with various fatty acids to form
several SL species. Ceramide is the central molecule which is generated
by de novo synthesis or formed by degradation from sphingomyelin
at plasma membrane level, while sphingosine is formed from ceramide by
ceramidase(6). Cytosolic conversion to their respective phosphorylated
forms, ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) and
further to other sphingolipids including glycosphingolipids constitute
the bioactives that are regulated by the various kinases, phosphatases,
hydrolases and lyases (Figure 1) . Activation of the pathway
occurs in response to a variety of cellular stresses due to UV
radiation, pathogen exposure, allergens and chemotherapeutic agents,
leading to the production of the bioactive lipid ceramide(7). Ceramide
and sphingosine are interconvertible components of the “sphingolipid
rheostat” that regulates immune function(8). These immune modulating
sphingolipids accumulate in cell membrane and compartmentalize
intracellularly to play a major role in immune cell trafficking,
inflammation, barrier cell integrity and cell survival(6,7,9).
In light of the above recent understanding from reports of systemic
allergic disorders, we decided to explore such bioactive lipids in the
ocular allergic disorder, specifically VKC. The etiopathogenesis of VKC
is still being explored. In addition, with the available reports in
literature, we are presently unable to explain the etiopathology of
refractoriness of this condition, barring reports of higher levels of
inflammatory cytokines in these severely affected eyes compared to the
less severe ones(10). We therefore specifically studied the sphingolipid
metabolism in patients with vernal keratoconjunctivitis.