I believe that the conjunctiva is the “next frontier” of dry eye study. Consider that dry eye is a multifactorial disease that affects one or more elements of the ocular surface functional unit, which includes the tear film, cornea, limbus, conjunctiva, and lid margin muco-epidermal junction as well as the lacrimal gland tubulo-acinar epithelia, the lacrimal drainage system, and the eyelids. The epithelia have an intense and continuous glycoprotein secretory activity integrated with the lacrimal fluid (Rolando et al, 2018).

The Importance of Mucins

Mucins are critical for tear film quality stability. They play important roles on the ocular surface in wettability, lubrication, and barrier function. Mucins are classified into two categories: secreted mucins and membrane-associated mucins. There are at least 20 mucin genes encoding different mucin gene products (Gipson, 2016). The most important secreted mucin on the ocular surface, MUC5AC, is delivered by the conjunctival goblet cells. Alteration of membrane-bound mucin expression on corneal and conjunctival epithelial cells and/or of gel-forming mucin secretion by goblet cells promotes ocular surface diseases.

Changes in the mucin layer may lead to enhanced tear evaporation contributing to tear hyperosmolarity, which has been associated with ocular surface inflammation. To follow, inflammatory mediators are considered to have a negative impact on goblet cell differentiation, proliferation, and mucin secretion. As a contributor to ocular surface immune homeostasis, goblet cell loss may contribute to the impaired ocular surface immune tolerance observed in dry eye disease (DED) (Baudouin et al, 2018). Mucin dysfunction and mucin-associated homeostasis imbalance, therefore, likely perpetuates the vicious cycle of DED.

Mucins are heavy molecular glycoproteins formed by numerous sugar chains linked to a core protein called apomucin (Moniaux et al, 2001). In the human conjunctiva, goblet cells that secrete MUC5AC are present in higher concentrations in the inferior nasal fornix near the tear drainage system (Kessing, 1968). They are also abundant in the lid wiper portion of the lid margins (Knop et al, 2011) to facilitate lubrication of the ocular surface during blinking (Knop et al, 2012). Eyelid movement during blinking evenly spreads MUC5AC secreted from the goblet cells into the lacrimal fluid over the entire ocular surface to maintain its wettability and lubrication. The number of conjunctival goblet cells and MUC5AC expression/secretion are decreased in dry eye patients (Hori, 2018).

Love the Conjunctiva

Mucin production therapies (i.e., secretagogues) for treating dry eye are available in Japan. Both drugs induce expression of MUC5AC from conjunctival goblet cells.

It is unknown whether changes in mucin expression on the ocular surface cause or result from dry eye; further study is needed to determine the true mechanism. Development of methods to study the conjunctiva differentiation will provide opportunities to treat human ocular surface diseases, particularly the drying and cicatrizing forms. Until then, I urge you to critically evaluate the conjunctiva via vital dye staining pattern assessment, physical characteristics (position, folds, laxity), and signs of inflammation (chemosis, injection) as you plan your course of dry eye therapy for patients. CLS

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