Wednesday, December 6, 2023
processing....
Symptoms of ocular disorders often overlap,[7**] sometimes making it difficult to accurately distinguish between the different forms of these diseases. In addition, patients may have concomitant nonallergic ocular disorders that present similar symptoms as allergic conjunctivitis, which could lead to misdiagnosis and inappropriate treatment. The immune responses of ocular allergies are complex, making it difficult for available treatments to target the initial pathophysiological mechanisms responsible for the symptoms. This situation explains why a recurrence of ocular allergic disease may occur soon after a patient stops treatment.[20] According to Bonini[6**] the term allergic conjunctivitis, although often synonymous with ocular allergy, does not sufficiently cover all allergic diseases of the eye. Further, classification and differential diagnosis of ocular allergy based on clinical presentation is not sufficient, as this situation only satisfies established eye examination parameters. Thus, a system of classifying ocular allergies based on the pathophysiology of these disorders may be more desirable and effective.[6**,8**]
Characterization of immune cells involved in allergic conjunctivitis has been further elucidated in the past year. A recent study suggests that CD8+ T cells promote the development of experimental allergic conjunctivitis in the induction phase, indicated by reduced conjunctival eosinophilic infiltration in ragweed-immunized/challenged CD8-deficient mice compared with wild type mice.[21] Another study found that thymus-derived CD4+CD25+ T cells suppress the development of experimental allergic conjunctivitis in mice sensitized/challenged with short ragweed.[22*] This suppression is suggested to be based on the observation of higher eosinophil infiltration levels, increased ragweed-specific IgE, and increased Th2 cytokine production in mice lacking CD4+CD25+ T cells.[22*,23] This study supports previous work, which demonstrated an association between the development of protective CD4+CD25+ T cells and the reduction of allergic conjunctivitis in a mouse model with chronic Ascaris infection.[24] It has also been indicated that the targeting of T-cell immunoglobulin and mucin domain-containing proteins (Tim) with antibody suppresses ragweed-induced experimental allergic conjunctivitis.[25*] These studies indicate potential roles that accessory T cells may have in allergic conjunctivitis, possibly stimulating the development of therapeutics dedicated to modulating the function of these cells.
Antigen-presenting cells play key roles in the initiation of the allergic cascade. As has been indicated in previous studies, conjunctival macrophages are a major source of antigen presentation in murine models of ocular allergy.[26] A recent study conducted by our laboratory suggests that dendritic cells may also participate in antigen presentation during allergic conjunctivitis.[27*] A product isolated from the pseudocoelomic fluid of adult Ascaris suum (PCF) has been shown to suppress allergic airway inflammation and allergic conjunctivitis in mouse models.[27*] PCF has also been shown to markedly downregulate antigen-induced dendritic cell activation in vitro. Taken together, these findings infer that the inhibition of dendritic cell activation may be a possible mechanism utilized for the suppression of allergic disease.[27*] Upon further characterization of the role that dendritic cells may have in allergic conjunctivitis, therapeutic modulation of dendritic cell activation and function may show promise in treating ocular allergic diseases.
Structural components of the ocular surface, including fibroblasts and epithelial cells, have also been shown to have very important roles in the modulation and enhancement of ocular allergy as well as in a patient’s susceptibility to reoccurring cases of allergic conjunctivitis.[19**,28,29] Fibroblasts have been shown to promote the formation of giant papillae as well as express adhesion molecules, extracellular matrix proteins, cytokines, and chemokines.[28] Notably, a recent study found that the chemokine production profile of conjunctival fibroblasts cultures has significant similarities to tear samples obtained from all subgroups of allergic conjunctivitis.[30**] Mediators present in tear samples from ocular allergy patients have been recently found to upregulate eosinophil adhesion to human conjunctival epithelial cells ex vivo, providing further insight into which adhesion factors (i.e. β2 integrins) may be responsible for eosinophilic infiltration to the conjunctiva.[31] Further analysis of the chemokines, adhesion molecules, and cytokines produced in these structural cells can help clarify the roles that these cells play in the pathogenesis of allergic conjunctivitis and provide insight into a patient’s susceptibility to ocular allergy upon reexposure to allergens.
