Immunopathology of Allergic Conjunctivitis

Abstract

Allergic conjunctivitis is predominantly an immunoglobulin E-mediated hypersensitivity reaction to environmental allergens. Allergic diseases affect >30% of the world’s population, of which 40% report associated ocular manifestations. Cellular and soluble mediators play a major role in the pathophysiology of allergic conjunctivitis. Mast cells, which are major effector cells of allergic conjunctivitis, undergo activation and degranulation to release histamine, tryptase, prostaglandins, leukotrienes, and cytokines. These mediators play important roles in immunopathological mechanisms that generate the clinical manifestations of allergic conjunctivitis. These clinical features include conjunctival hyperaemia, chemosis, tearing, itching, papillae, mucus discharge, and eyelid oedema. Histamine mediates the early phase of the allergic immune response, whereas lipid mediators and cytokines are involved in the late phase of the immunopathology of allergic conjunctivitis. Current management of allergic conjunctivitis includes non-pharmacological approaches such as allergen avoidance and palliative therapy, whereas pharmacological therapeutic modalities may include antihistamine–mast cell stabiliser combination ophthalmic formulations and allergen-specific immunotherapy. Furthermore, as cellular and soluble mediators play a pivotal role in the immunopathogenesis and immunopathology of allergic conjunctivitis, development of immunotherapeutic and pharmacotherapeutic agents specific to these mediators can enhance the therapeutic index and safety profile of anti-allergy treatment.

Ocular surface itch and pain: key differences and similarities between the two sensations

“…A push to better understand mechanisms that contribute to the acute to chronic pain transition, molecules involved in the maintenance of chronic pain, and diagnostic strategies to identify neuropathic pain will hopefully lead to improved treatment strategies that deliver personalized targeted therapies. As exploration continues in addressing ocular itch and pain, further characterization of these abnormal sensations can help guide diagnostics and treatment strategies [10,30,31,44].…”

Vernal Keratoconjunctivitis: Immunopathological Insights and Therapeutic Applications of Immunomodulators

“…Patients with VKC present with complaints of intense ocular pruritis, which could be attributed to the interaction between histamine and histamine receptor 1 expressed on the conjunctival sensory nerve fibers [ 74 , 75 ]. The interaction between IL-31, a cytokine released by traumatized ocular surface epithelial cells, degranulated mast cells, eosinophils, and Th2 cells and their receptors expressed on sensory nerve fibers in the conjunctiva are also responsible for this intense itch sensation [ 76 , 77 ].…”

“…IL-13 is a pleiotropic cytokine secreted by Th2 cells and degranulated mast cells. It can induce the hyperplasia of goblet cells located in the conjunctival epithelium, as well as induce the hypersecretion of mucin from these activated conjunctival goblet cells [ 4 , 74 , 90 ]. Furthermore, IL-9 also induces the hyperplasia of goblet cells [ 91 ].…”

“…Furthermore, IL-9 also induces the hyperplasia of goblet cells [ 91 ]. Additionally, mucoid discharge has been shown to occur when histamine binds to histamine receptors expressed on goblet cells [ 74 , 92 ]. Thus, Th2- and Th9-derived cytokines are contributors to the complaint of mucoid discharge.…”

Cytokines in Allergic Conjunctivitis: Unraveling Their Pathophysiological Roles

“…Overexpression of IL-13 is linked to the development of pathophysiological features consistent with allergic conjunctivitis including the hyperplasia of goblet cells in the epithelial layer of the conjunctiva [ 14 , 137 ]. It is of note that mucoid discharge does occur in allergic conjunctivitis due to IL-13-induced hypersecretion of mucin from activated goblet cells [ 48 , 138 , 139 ]. Additionally, IL-13 acts on epithelial cells and smooth muscle cells to promote allergic inflammation [ 18 ].…”