|
| Dry Eye |
|
| |
|
|
The Definition of Dry Eye
Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.
Aqueous Tear-Deficient Dry Eye (Tear Deficient Dry Eye; Lacrimal Tear Deficiency)
Aqueous tear-deficient dry eye implies that dry eye is due to a failure of lacrimal tear secretion. In any form of dry eye due to lacrimal acinar destruction or dysfunction, dryness results from reduced lacrimal tear secretion and volume. This causes tear hyperosmolarity, because, although the water evaporates from the ocular surface at normal rates, it is from a reduced aqueous tear pool. Tear film hyperosmolarity causes hyperosmolarity of the ocular surface epithelial cells and stimulates a cascade of inflammatory events involving MAP kinases and NFkB signaling pathways and the generation of inflammatory cytokines. When lacrimal dysfunction is due to lacrimal gland infiltration and inflammation, inflammatory mediators generated in the gland are assumed to find their way into the tears and be delivered to the ocular surface. However, when such mediators are detected in the tears, it is not usually possible to know whether they derive from the lacrimal gland itself or from the ocular surface (conjunctiva and cornea).
Evaporative Dry Eye
Evaporative dry eye is due to excessive water loss from the exposed ocular surface in the presence of normal lacrimal secretory function. Its causes have been described as intrinsic, where they are due to intrinsic disease affecting lid structures or dynamics, or extrinsic, where ocular surface disease occurs due to some extrinsic exposure. The boundary between these two categories is inevitably blurred.
Novel Targets For The Treatment Of Dry Eye
Changes in the stability of the tearfilm have long been associated with mucin production and secretion from the conjunctival goblet cells. More recently it has been reported that secretion of mucin MUC 5AC from the conjunctiva can be influenced by neurotrophins such as nerve growth factor (NGF) and brain-derived growth factor (BDNF).
Small Molecule Mucin Secretagogues
Mimetogen has developed a family of small molecule tyrosine kinase receptor agonists that are powerful mucin secretagogues. The compounds have been shown to stimulate mucin MUC 5AC secretion from conunctival goblet cells. Further efficacy and toxicology studies will help choose the lead compound that will enter GLP toxicology and clinical trials in 2009.
|
| |
|
|
|
| 
|
1000 de La Gauchetière Street West, Suite 900. Montréal, Québec, H3B 5H4, Canada
|
|
|
|
|
