| Glaucoma is the second leading cause of irreversible blindness in the United States. It is characterized by progressive loss of retinal ganglion cells with associated loss of vision that is often coupled with elevated intraocular pressure (IOP). Primary open-angle glaucoma (POAG) is the most common form of glaucoma that is caused by increased resistance in the conventional outflow pathway. Unfortunately, the biology and physiology of the human outflow tract and its role in ocular hypertension remains poorly understood. The purpose of our study is to investigate the pharmacological regulation of aqueous outflow in human conventional outflow pathway using anterior segment perfusion model.; Human anterior segments were perfusion cultured for one or two weeks while the functional response of cells in the conventional outflow pathway was measured by recording the pressure change in the anterior chamber and the outflow facility was calculated. In addition, the central corneal thickness was recorded every 24 hours during the perfusion and the relationship between functional corneal endothelial cells and viable trabecular meshwork cells were examined. After perfusion-fixation, drainage tissues of each anterior segment were histologically graded. At last, an effective anti-glaucoma agent---bimatoprost and a prostamide specific antagonist were introduced to the anterior segment perfusion model and their pharmacological function in regulating outflow facility in human conventional outflow pathway was investigated. We attained stable outflow facility from the perfusion culture of anterior segment and found that the outflow pathway tissues were viable after dissection and weeks of incubation in the perfusion system. In addition, we found that there was a recovery in central corneal thickness over time of perfusion and this recovery correlated with the viability of the trabecular meshwork tissues. Finally, we observed that bimatoprost increased outflow facility and a prostamide specific antagonist significantly attenuated this effect.; In conclusion, these studies demonstrate that the tissues of conventional outflow pathway are viable after weeks of perfusion and the function of corneal endothelial cells reflects the viability of the trabecular meshwork cells in conventional outflow pathway. Finally, our data supports that bimatoprost increases outflow facility by targeting a novel receptor in the conventional outflow pathway. |
