The research objective is to demonstrate that the adrenergic nerves in the ciliary processes have a regulatory function in ciliary epithelial secretion of aqueous humor. Aqueous humor formation rate, intraocular pressure, and anterior chamber volume will be measured non-invasively using fluorophotometry, tonometry and photogrammetrically. Pharmacological studies will involve changing the activity of the ciliary epithelial cells with drugs that stimulate or block their post-junctional receptors. Neurotransmitter release from the sympathetic nerves in the ciliary processes will be stimulated and inhibited using drugs that interact with receptors on the sympathetic nerve terminals. Neurophysiological studies will investigate the effects of chronic stimulation of the cervical sympathetic nerves and of ganglionectomy on aqueous humor flow. The effects of beta-adrenergic desensitization and supersensitivity on ciliary epithelial secretion will be studied. Ciliary epithelial cells internalize plasma membrane in response to stimulation with beta-adrenergic drugs (eg. isoproterenol). This internalization of membrane is probably moving receptors into the cell and may be part of the desensitization mechanism. Using electrical stimulation of the sympathetic nerves and transmission electron microscopy, we will investigate whether endogenous norepinephrine from in situ sympathetic nerves induces plasma membrane internalization and if this is associated with a decrease in aqueous humor formation. The health-related goal of this research is to define the cell biology and pharmacology of the ciliary epithelium and identify parameters regulating secretion of aqueous humor that are pharmacologically manipulatable. Thus, glaucoma-related ocular hypertension can be medically managed and vision loss and surgery prevented.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004914-08
Application #
3259540
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-02-01
Project End
1993-01-31
Budget Start
1991-02-01
Budget End
1993-01-31
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Schepens Eye Research Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02114
Murray, D L; Bartels, S P (1993) The relationship between aqueous humor flow and anterior chamber protein concentration in rabbits. Invest Ophthalmol Vis Sci 34:370-6
Freddo, T F; Bartels, S P; Barsotti, M F et al. (1992) Morphologic correlations with fluorophotometric data from monkey eyes with anterior uveitis. Invest Ophthalmol Vis Sci 33:1642-9
Barsotti, M F; Bartels, S P; Freddo, T F et al. (1992) The source of protein in the aqueous humor of the normal monkey eye. Invest Ophthalmol Vis Sci 33:581-95
Liu, J H; Dacus, A C; Bartels, S P (1991) Adrenergic mechanism in circadian elevation of intraocular pressure in rabbits. Invest Ophthalmol Vis Sci 32:2178-83
Bartels, S P; Pawlowski, A M (1990) Chronic electrical stimulation of sympathetic nerves: effects on blood-aqueous barrier. Curr Eye Res 9:927-34
Freddo, T F; Bartels, S P; Barsotti, M F et al. (1990) The source of proteins in the aqueous humor of the normal rabbit. Invest Ophthalmol Vis Sci 31:125-37
Barsotti, M F; Bartels, S P; Kamm, R D et al. (1990) Background-protein effects on fluorophotometric data. Invest Ophthalmol Vis Sci 31:2046-50
Liu, J H; Dacus, A C; Bartels, S P (1989) Thyrotropin releasing hormone increases intraocular pressure. Mechanism of action. Invest Ophthalmol Vis Sci 30:2200-8
Bartels, S P (1988) Aqueous humor flow measured with fluorophotometry in timolol-treated primates. Invest Ophthalmol Vis Sci 29:1498-504
Higginbotham, E J; Lee, D A; Bartels, S P et al. (1988) Effects of cyclocryotherapy on aqueous humor dynamics in cats. Arch Ophthalmol 106:396-403

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