Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology

Abstract

Trehalose is a naturally occurring disaccharide comprised of two molecules of glucose. The sugar is widespread in many species of plants and animals, where its function appears to be to protect cells against desiccation, but is not found in mammals. Trehalose has the ability to protect cellular membranes and labile proteins against damage and denaturation as a result of desiccation and oxidative stress. Trehalose appears to be the most effective sugar for protection against desiccation. Although the exact mechanism by which trehalose protects labile macromolecules and lipid membranes is unknown, credible hypotheses do exist. As well as being used in large quantities in the food industry, trehalose is used in the biopharmaceutical preservation of labile protein drugs and in the cryopreservation of human cells. Trehalose is under investigation for a number of medical applications, including the treatment of Huntington's chorea and Alzheimer's disease. Recent studies have shown that trehalose can also prevent damage to mammalian eyes caused by desiccation and oxidative insult. These unique properties of trehalose have thus prompted its investigation as a component in treatment for dry eye syndrome. This interesting and unique disaccharide appears to have properties which may be exploited in ophthalmology and other disease states.

Keywords: cells; desiccation; disaccharide; trehalose.

Figure 1

Structure of trehalose. Registry number: 99-20-7; Molar mass: 342.296 g/mol (anhydrous); 378.33 g/mol (dihydrate); molecular structure: α-D-glucopyranosyl α-D-glucopyranoside (α,α-trehalose).

Figure 2

Trehalose protects against corneal damage due to desiccation. Corneal fluorescein staining following exposure to a desiccant environment. Mice were exposed to a desiccating environment for 21 days and then received treatment with phosphate-buffered saline, trehalose eyedrops, or mouse serum eyedrops for 14 days. A) Control mice, B) 21 days desiccation without treatments, C) and D) seven and 14 days’ desiccation with trehalose treatment, E) and F) seven and 14 days desiccation’ with mouse serum treatment, G) and H) seven and 14 days’ desiccation with phosphate-buffered saline treatment. Copyright© 2010. Elsevier. Reproduced with permission from Chen W, Zhang X, Liu M, et al. Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis. Exp Eye Res. 2009;89: 311–318.

Figure 3

Rabbit eyes following irradiation with ultraviolet for four days, with concurrent treatment of trehalose or buffered saline. A) Corneal vascularization and loss of transparency in saline-treated eye; B) and C) eyes treated with trehalose, showing less vascularization and retention of transparency; and D) normal (nonirradiated) cornea. Copyright© 2010. Histology and Histopathology. Reproduced with permission from Čejková J, Čejka Č, Ardan J, Širc J, Michálek J, Luyckx J. Reduced UVB-induced corneal damage caused by reactive oxygen and nitrogen species and decreased changes in corneal optics after trehalose treatment. Histol Histopathol. 2010;25:1403–1414.