The secretion of fluid by the ciliary body requires transepithelial transport of solutes, with water following osmotically. The experiments proposed in this project will examine the ionic conductances that control the movement of ions across the cell membrane, and thus control the secretion of fluid by the ciliary body. The principal focus is to determine how neurotransmitters and hormones affect these ionic conductances which may help explain the regulation of intraocular pressure by these agents. The intracellular signaling pathways that link neurotransmitter or hormone receptors to the ion channels of the ciliary epithelial cells will also be investigated. Because transport of chloride ions is a vital component of the transepithelial fluid transport, one aspect of the proposal focuses on chloride channels and their regulation. The ionic mechanisms will be investigated in both the nonpigmented and the pigmented epithelial cell layers. The overall goal is to establish the cellular mechanisms governing epithelial transport in the ciliary body in order to gain a greater understanding of the control of intraocular pressure and of the signaling pathways which may provide important targets for drugs that can reduce aqueous inflow.
Matthews, G (1996) Neurotransmitter release. Annu Rev Neurosci 19:219-33 |
Botchkin, L M; Matthews, G (1995) Swelling activates chloride current and increases internal calcium in nonpigmented epithelial cells from the rabbit ciliary body. J Cell Physiol 164:286-94 |
Botchkin, L M; Matthews, G (1994) Voltage-dependent sodium channels develop in rat retinal pigment epithelium cells in culture. Proc Natl Acad Sci U S A 91:4564-8 |
Botchkin, L M; Matthews, G (1993) Chloride current activated by swelling in retinal pigment epithelium cells. Am J Physiol 265:C1037-45 |