A Potential Target Site To Decrease Outflow Resistance
Haiyan Gong, MD, PhD Trustees of Boston University
SummaryThe goal of this study is to better understand the mechanisms involved in the regulation of aqueous outflow resistance in non-human and human eyes and to determine whether the connectivity between the inner wall of Schlemm's canal and underlying matrix in a portion of the eye, termed the trabecular meshwork, can be targeted to reduce outflow resistance, thus lowering intraocular pressure (IOP) in human eyes as it occurs in non-human eyes.
Project DetailsThe reason(s) for increased aqueous humor outflow resistance in primary open angle glaucoma (POAG) eyes remains unknown. Currently, lack of a thorough understanding of the mechanism responsible for regulating aqueous humor outflow resistance hinders the development of effective anti-glaucoma therapy aimed at “trabecular outflow”, through which the majority of normal aqueous outflow exits the eye. In our preliminary studies of non-human eyes we found that the available area for aqueous outflow increases when outflow resistance decreases after short term perfusion with a cell structure disrupting agent, Y27632. This suggests a relationship between the available area for aqueous outflow and outflow resistance, which was regulated by a structural change in the aqueous drainage system. Similar changes were not found in cadaver human eyes under a similar experimental condition. We are attempting to understand the mechanism causing these structural changes in non-human eyes. We will take the non-human results and use this as a means to induce similar changes in human eyes in order to develop a new anti-glaucoma treatment. We will use our newly developed methods to study the following Specific Aims:
1) To determine whether a type of drug called Y27632, a Rho-kinase inhibitor and the cell-structure disrupting agent, can further decrease outflow resistance after the structural change has been induced after long-term perfusion ( washout effect) in non-human eyes;
2) To determine whether a similar structural change can be induced to decrease outflow resistance using different experimental conditions in human eyes;
3) To determine whether decrease in aqueous humor outflow resistance under two experimental conditions (long-term perfusion and treatment by Y27632) share a similar mechanism.