Glucocorticoids, Growth Factors, and the TM

Pressure inside the eye is maintained by a constant production of fluid within the eye. In the front portion of the eye, the fluid (aqueous humor) is produced throughout the day and functions to bathe and to nourish structures (e.g. lens and cornea) in the front of the eye. Aqueous humor exits the eye through a drain (the trabecular meshwork). In a normal eye there is ample drainage to handle fluid production. In glaucoma, the drainage system is insufficient to handle the fluid produced. Thus, in most cases of glaucoma there is an increase in intraocular pressure which damages cells in the retina and eventually causes blindness. Most non-surgical treatment for glaucoma (i.e. eye drops) is directed towards reducing the production of aqueous humor and thus lowering the pressure inside the eye. We know very little about the normal function of the site of fluid drainage. Substances called growth factors are made by various cells in the body and function to stimulate cell division, cell movement and cell function. The aqueous humor which passes through the trabecular meshwork is known to contain these substances. They are thought to be important in maintaining the normal function of the trabecular meshwork. In addition cells within the trabecular meshwork may also produce local growth factors to maintain normal aqueous humor drainage. A family of steroid hormones called glucocorticoids have been implicated in some types of glaucoma. The cause of the elevated intraocular pressure associated with glucocorticoid treatment is similar to that in glaucoma thus the treatment of trabecular meshwork cells has been used as a model system to study glaucoma. The overall objective of the application is to further our knowledge of the role glucocorticoids play in inducing glaucoma.

Hypothesis

The working hypothesis of this application is that the presence and/or the amounts of growth factors within human trabecular meshwork cells is altered after exposure to glucocorticoids.

Specific Aims

The following specific aims have been developed to test the working hypothesis: (1) to determine if growth factors or growth factor receptor production by human trabecular meshwork cells is altered by exposure to the glucocorticoid dexamethasone (DEX) and (2) to use a anterior eye model system which duplicates the normal eye and contains a whole trabecular meshwork to determine if the fluid passing through this structure is altered by the hormone.

Long Term Goals

The significance of the study is that it will increase our basic knowledge of the role growth factors play in the pathology of human trabecular meshwork cells. This type of basic information has the potential to lead to new and innovative methods to prevent, treat, or reverse changes in the human trabecular meshwork within the glaucoma patient.