Mechanisms at play
Some of the aforementioned mechanisms may involve the integrity of the epithelial barrier. Whereas the junctional complexes are intact in the normal conjunctival epithelium, denying allergens entry, epithelial barrier dysfunction may be induced by endogenous proteases (e.g., metalloproteases) and environmental assailants including some viruses; components of air pollution; cigarette smoke; house dust mites; and pollens, which have intrinsic protease activity.
Initially, epithelial cells were considered to be a passive barrier impeding allergen penetrance, but we know now that they may recognise allergens and mount an innate immune response with multiple factors such as cytokines, alarmins and endogenous danger signals that activate the dendritic cell (DC) network and other innate immune cells.7 As a consequence, local immune responses may be initiated, beginning the transition from innate to adaptive immunity.
In particular, allergens induce the production of reactive oxygen species, which activate DC and epithelial cells through NF-kB activation. The innate immunity of epithelial cells not only recognises microbial invasion but may also respond to pollen components from plants, triggering inflammation.7
In fact, in response to allergen recognition, epithelial cells promote Th2 immunity through activation of DCs, by activating innate immune cells such as ILC2s, which can help DCs to polarise Th2 responses in naive T cells.8
Increased expression of heat-shock proteins (HSPs) in VKC patients was recently described by Leonardi et al.9 The HSP-chaperones are highly conserved during evolution and play essential roles in cell survival; however, they are also implicated in the pathogenesis of various diseases such as some types of cancer and inflammatory and autoimmune disorders.
Expression of HSPs is induced by environmental and oxidative stress and forms a link between adaptive and innate immunity. Increased HSP levels induced by agents known to initiate or aggravate VKC, such as histamine, cytokines and UV-B, indicate an active interaction between the chaperoning and the immune systems, with perhaps a mutual modulatory role between the two systems.
HSP27, HSP40, HSP70 and HSP90 seem to be actively involved in VKC, where they may initiate and perpetuate inflammation.
New mass spectrometric techniques to analyse peptide profiles in human tears may elucidate differences between healthy subjects and patients affected by different phenotypes of ocular allergy and possibly identify target proteins that might be of use in the diagnosis, prognosis and management of VKC and other inflammatory ocular surface conditions.
For example, hemopexin, transferrin, mammaglobin-B and secretoglobin 1D were found to be significantly overexpressed in VKC samples and dramatically reduced after treatment with topical cyclosporine.10