Measurement of Fluid Flow Across the Ocular Ciliary Body

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Glaucoma is a family of diseases characterized by degenerative optic neuropathy, usually related to an elevation in intraocular pressure (IOP), resulting in irreversible blindness. It is a leading cause of vision loss worldwide. Given that elevated IOP is the most common factor associated with retinal damage, pharmacological treatments directed at glaucoma have focused upon increasing the drainage of the aqueous humor or reducing its production by the ciliary epithelium. Yet, a clear understanding of the physiological mechanisms by which the aqueous is produced remains elusive. The driving forces for fluid secretion across the ciliary epithelium are the osmotic gradient created by ionic transport and a hydrostatic pressure difference, with their relative contributions undetermined. Although extensive work has identified the ions that are transported for the creation of the osmotic gradient, published data suggest that the transport rates may be insufficient to account for the rate of fluid production (implying the importance of ultrafiltration) and a transport model consistent with all of the available experimental data does not exist. This may be due to the complexity of the ciliary epithelium as well as variations in transport elements among the species studied. Actual measurements of fluid movement across the isolated ciliary epithelium have not been attempted as commonly done with other water transporting epithelia such as those of the kidney, urinary bladder and corneal endothelium. Our preliminary, experiments show that we can measure fluid transport in this isolated tissue. Therefore, the aims of this proposal are 1) to measure fluid transport across isolated ciliary epithelia from bovine and rabbit, two well characterized tissues manifesting distinct electrolyte transport properties; 2) to study the effects of stimulants and inhibitors of electrolyte transport on the rate of fluid transport in the two model tissues; and 3) to study the effects of ion replacement and depletion on the rate of fluid transport. These relatively simple experimental approaches will fill a void in the present understanding of ciliary epithelial physiology and should provide a quantification of the contribution of ionic transport to aqueous formation.