Article

READER AND INDUSTRY FORUM

TREHALOSE: A SUBSTRATE WITH OCULAR SURFACE BENEFITS

As attempts to decrease dry eye-related inflammation and improve healthy tear production are pursued, it is critical to also support the ocular surface to repair any compromised tissue. Artificial tears provide this support and are an integral factor to managing the signs and symptoms of dry eye disease (DED). Components of modern day artificial tears are remarkably sophisticated. Carboxymethylcellulose, a mucoadhesive solution, is used to increase the resident time on the ocular surface (Garrett et al, 2007). Hyaluronic acid (HA), with its viscoelastic properties, is effective in keeping the eye lubricated by reducing shear forces (Aragona et al, 2014). Trehalose, a naturally occurring sugar, has also shown promise for its protective properties against desiccation as an inactive substance that serves as the vehicle (excipient) for artificial tear formulations.

Trehalose, a disaccharide, has been found in many organisms such as plants, insects, yeasts, invertebrates, bacteria, and fungi (Argüelles, 2000). Trehalose contributes to the homeostasis of these organisms, playing different roles in their survival. For example, heat, drying, and oxidative stress induce trehalose to be synthesized and stored (Jain and Roy, 2009); that storage may be as high as 10% to 20% of the organism’s dry weight (Elbein et al, 2003). The accumulation within the cells protects proteins and membranes from denaturation.

Trehalose is not synthesized in mammals, although there is a trehalose enzyme that has been identified in human kidney and intestinal cells (Elbein et al, 2003). This suggests that humans have been exposed to trehalose and in direct contact with it for some time. Understanding the role and applications of trehalose is well established in the food and cosmetic industries (Luyckx and Baudouin, 2011).

Trehalose in the Eye

Trehalose has been used as an excipient in intravitreal formulations (Luyckx and Baudouin, 2011). When tested on human corneal epithelial cells, trehalose has been effective in protecting the cells from dehydration by preserving their physiological morphology (Hill-Bator et al, 2014). It protects the cell membrane, maintaining its properties and preserving the phospholipid bilayer. It is also most effective at stabilizing cell proteins to maintain cell integrity (Jain and Roy, 2009). This is achieved by physically shielding the proteins or by a bonding interaction between trehalose and the structure of the proteins themselves (Jain and Roy, 2009). These bioprotective and osmoprotective characteristics are in part why trehalose is effective as part of a comprehensive dry eye treatment regimen.

Ingredient in Lubricating Eyedrops

Artificial tears with trehalose are available in parts of Europe and Canada as preservative-free multidose formulations. Some studies have found that trehalose improves symptomatic relief for moderate-to-severe dry eye patients (Pinto-Bonilla et al, 2015; Chiambaretta et al, 2017) as well as for those who have undergone laser-assisted in situ keratomileusis (LASIK) (Mateo Orobia et al, 2017).

One study presented at the Association for Research in Vision and Ophthalmology 2017 annual meeting supports a promising future for trehalose, such as combining it with flaxseed oil in a novel eyedrop formulation that can improve both dry eye signs and symptoms (Hom et al, 2017). The anhydrobiotic characteristic of trehalose offers a unique advantage in artificial tear formulations for the management of DED and is likely to be prominent in future artificial tear formulations. CLS

For references, please visit www.clspectrum.com/references and click on document #266.