The Role of RPE Fluid Transport in Aqueous Humor Dynamics

The pressure in the eye is maintained by a balance between the production and drainage of an intraocular fluid. When the drainage rate is decreased too much, the pressure in the eye will increase. If the increased pressure is too high for too long, then damage may occur to the optic nerve which can result in vision loss. This condition is called glaucoma and is a leading cause of blindness in this country. Because it is so important to maintain the intraocular pressure at a stable healthy level, much work has been done to better understand the circulation of the fluid in the eye. Most scientists believe there are two important drainage pathways for this fluid which are found in the front part of the eye but there is a third drainage pathway in the back of the eye across the retina that is generally ignored. In this project, we will study the production and drainage of the intraocular fluid with special emphasis on the drainage across the retina. We will measure the normal rate of fluid movement in this direction and try to stimulate its flow so that more fluid will be drained and the pressure in the eye can decrease. We will test two different drugs that have been used for years in the treatment of glaucoma. One of these drugs is acetazolamide (Diamox). It is believed to work by decreasing aqueous production but it may also work by increasing drainage across the retina. The other drug is epinephrine (Glaucon). It is believed to work by increasing drainage through the front part of the eye but there is growing evidence that it may also increase drainage across the retina. We will use the cat to measure the fluid production and drainage through the anterior and posterior outflow routes. The lens and vitreous will be removed and replaced with an oil in which to selectively block one or all drainage routes. Using fluorescent dyes or simply by collecting all aqueous that is produced, we will be able to measure production rate and drainage through either the front or back of the eye. The experiments will be repeated after drug treatment. From these studies we hope to get a clearer picture of how fast aqueous is produced and how much of it drains through which pathway. Many glaucoma drugs have been developed to decrease the intraocular pressure, some work by decreasing aqueous production and some have been designed to increase the drainage through the front of the eye. If the posterior drainage can be increased by drugs, then this may provide an new way to treat glaucoma. For people whose glaucoma is not being successfully treated with the usual drugs, agents that increase posterior drainage might become a new option for them.