Role of AMCase in the Allergic and Non Allergic Ocular Pathologies

Abstract

Chitin is abundant in the structural coatings of fungi, insects, and parasitic nematodes, but it is not produced in mammals. The host defense against chitin-containing pathogens include production of chitinases. An acidic mammalian chitinase (AMCase) is produced in human epithelial cells of lower airways and conjunctiva via a Th2-specific, IL-13-dependent pathway and seems to be associated to asthma and allergic ocular pathologies. The role of AMCase in allergic disease is only at beginning and many issues open new possibilities for its control using specific inhibitors of AMCase activity or modulating its expression. In patients with vernal keratoconjunctivitis (VKC) and with season allergic conjunctivitis (SAC) the level of AMCase activity in the tears was found significantly elevated when compare to healthy controls and the highest levels were found in VKC. When RNA was extracted by conjunctival epithelial cells of these patients, the Real Time PCR measurement confirmed that the mRNA expression correlates with tear AMCase activity and the expression was significantly higher in VKC and SAC respectively. Also Receiver Operating Characteristic (ROC) analysis demonstrated that the sensitivity and specificity of AMCase measurement were 100% respectively, addressing the use of AMCase assay in the biochemical diagnosis of VKC and SAC. Recent studies in rabbit, where a reactive uveitis was induced by LPS injection in eye’s anterior chamber, confirmed that increased AMCAse activity was measurable in tears and that epithelial cells of conjunctiva express specific mRNA. A well as it was previously demonstrated in experimental model of mouse asthma, the inflammatory reaction induced by LPS was controlled by the chitinase inhibitor and steroid, instilled at 3 hr interval in conjunctival sacs. In dry eye, another pathologies where the role of innate immunity is sustained by AMCase secretion, an increased AMCase activity was documented and the specific mRNA expressed by epithelial conjunctival cells. In this pathology the eye inflammation can be ascribed to a common mechanism mediated by AMCase, via a Th 2 specific, IL-13 dependent way. In synthesis AMCase may be considered an important mediator in the pathogenesis of Th2 inflammation eye’s diseases, suggesting its potential diagnostic and therapeutic utility.