Dry Eye Dx and Tx
The Role of Mucins in Ocular Health
By Katherine M. Mastrota, MS, OD, FAAO
The March 2011 report of the Workshop on Meibomian Gland Dysfunction (Nichols et al, 2011) is a state-of-the-art account of meibomian gland dysfunction, especially as it relates to dry eye disease. The report recognizes the critical importance of the tear film's lipid layer, which is generated by the meibomian glands. Of equal importance to a healthy ocular surface, clear vision and ocular comfort, however, is the proper balance and functioning of the ocular surface's mucins. This column provides an overview of the role of mucins in ocular health.
Mucins are a family of complex, high-molecular-weight, heavily glycosylated (carbohydrate-attached) proteins produced by epithelial tissues. The myriad possibilities of carbohydrate chain attachment allow for a diverse complement of mucins. This dense “sugar coating” of mucins gives them considerable waterholding capacity. The high water content of mucins provides a medium through which nutrients, salts and gases can pass, a property critical for the avascular cornea of the eye (Mantelli and Argüeso, 2008). In addition, the adhesive properties of mucin molecules are core in their capacity as physical defenders of epithelial tissue, including that of the eye.
About 20 basic types of epithelial mucin have been identified in the human body. They are generally classified according to their physiologic functions and divided into two classes: cell surface-associated (or tethered) and secreted mucins. Secreted mucins are further divided into two subcategories: soluble and gel-forming mucins. Gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6, MUC19) are key components of most gel-like secretions, serving functions from lubrication to cell-signaling to the formation of chemical barriers.
Ocular Surface Mucins
To date, at least eight mucins have been found in the ocular surface epithelium (Wang et al, 2009). Conjunctival goblet cells secrete the gel-forming mucins MUC5AC and MUC2, whose xpression on the ocular surface is limited to the goblet cells (Inatomi et al, 1996). The conjunctival and corneal epithelia produce membrane-spanning mucins (MUC1, MUC4 and MUC 16) that form the glycocalyx and anchor the mucin layer to the naturally hydrophobic corneal surface (Inatomi et al, 1996; Gibson, 2004), rendering it hydrophilic. MU5AC, along with other soluble mucins, interact with the membrane-bound mucins and the tear's aqueous layer to form a water-trapping gel.
Mucins are responsible for tear film viscosity, protection of the ocular surface against the shear force of blinking, and lowering surface tension. Mucins clear allergens and debris from the ocular surface and, most likely, act as pathogen barriers. They may also serve as tear-film sensors, signaling changes in osmolarity (De Nadal et al, 2007).
Addressing Mucin Dysfunction
Topical cyclosporine, which has been demonstrated to increase conjunctival goblet cell density (Kunert et al, 2002), remains a proven treatment for dry eye. Therapies under development that address mucin dysfunction, whether it is primary or secondary to other forms of dry eye disease, hold promise in the ongoing quest for options to effectively manage ocular surface disease. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #194.
Dr. Mastrota is secretary of the Ocular Surface Society of Optometry. She is center director at the New York office of Omni Eye Services and a consultant to Allergan, B+L, Ista Pharmaceuticals, Merck, Noble Vision and Ocusoft. Contact her at firstname.lastname@example.org.