Long-term objective of this proposal is the investigation of cellular mechanisms relating to the production of aqueous humor by the ciliary epithelium.
Specific aims are the in vitro electrophysiologic study of transport processes on isolated preparations of the ciliary epithelium. These experiments will furnish information on normal physiological mechanisms and pharmacological-induced alterations involved in the active production of aqueous humor. Reduction of aqueous humor formation by medical therapy is a frequent treatment of the elevated intraocular pressure associated with glaucoma. Knowledge regarding cellular mechanisms responsible for aqueous humor production will provide insights into the normal rate of aqueous humor formation and possible pharmacologic mechanisms for the reduction in the rate of aqueous humor production. Isolated ciliary body preparations are mounted for measurement of transepithelial electrical parameters (potential difference, short-circuit current), net fluid transport, and unidirectional fluxes. These studies represent a consolidation of active transport and fluid flow in a tissue preparation maintaining the normal anatomic relationships between the double epithelial layers of the ciliary processes. Conventional micropipet impalement studies for measurement of membrane potential are performed in conjunction with the transepithelial measurements. These studies provide information on individual ciliary epithelial cells in relationship to ion movements and transport systems. In addition, intracellular iontophoretic injection of the fluorescent dye Lucifer Yellow is performed to study gap junctions which provide a pathway for intercellular communication (cell- cell coupling), thereby allowing cells to function as a syncytium. Electrophysiologic investigations are used to study the following classes of drugs: (i) halogenated anesthetic agents, (ii) adrenergic agonists and the interaction of neuropeptide Y with the adrenergic agonists, (iii) barbiturates, and (iv) sodium azide. These experiments will furnish information on mechanisms involved in the active production of aqueous humor and may result in new and unique antiglaucoma agents designed to inhibit the different sequential steps in aqueous humor production.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005240-17
Application #
2710871
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1990-01-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
2000-06-30
Support Year
17
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Oh, J; Krupin, T; Tang, L Q et al. (1994) Dye coupling of rabbit ciliary epithelial cells in vitro. Invest Ophthalmol Vis Sci 35:2509-14
Carre, D A; Tang, C S; Krupin, T et al. (1992) Effect of bicarbonate on intracellular potential of rabbit ciliary epithelium. Curr Eye Res 11:609-24
Yantorno, R E; Carre, D A; Coca-Prados, M et al. (1992) Whole cell patch clamping of ciliary epithelial cells during anisosmotic swelling. Am J Physiol 262:C501-9
Krupin, T; Wax, M B; Carre, D A et al. (1991) Effects of adrenergic agents on transepithelial electrical measurements across the isolated iris-ciliary body. Exp Eye Res 53:709-16
Tang, L Q; Krupin, T; Milner, M et al. (1991) Halogenated inhalation anesthetic agents decrease transepithelial electrical measurements across the isolated iris-ciliary body. Invest Ophthalmol Vis Sci 32:1912-5
Yantorno, R E; Coca-Prados, M; Krupin, T et al. (1989) Volume regulation of cultured, transformed, non-pigmented epithelial cells from human ciliary body. Exp Eye Res 49:423-37
Krupin, T; Wax, M; Moolchandani, J (1986) Aqueous production. Trans Ophthalmol Soc U K 105 ( Pt 2):156-61