The long term objective of this proposal is to learn whether humoral mediators can influence or regulate intraocular pressure in normal and/or glaucomatous eyes. Evidence from clinical and laboratory sources indicates that intraocular pressure can vary in a circadian rhythm, fall in pregnancy, and fall in response to agents administered systemically that stimulate the production of cyclic AMP in ciliary epithelia, the tissue secreting aqueous humor.
The specific aim of this research is to follow up our observation that certain glycoprotein hormones, in concentrations very similar to circulating levels of hormones found in vivo can reduce intraocular pressure. Studies will be initiated with HCG. The physiologic and cellular site of action will be determined and the chemical mechanism for the reduction of intraocular pressure be determined. Additional information from other glycoproteins and analogs of these and of HCG will be used to analyze the site of the response and its biochemical mechanisms. This proposal is consistent with the program base of the N.E.I. national plan for vision research of the glaucoma panel in its study of 1) cellular mechanisms of drug action to alter rate of inflow of aqueous humor, 2) the physiology and pathophysiology of aqueous humor inflow in hypotony, and 3) the cell biology of tissues involved in aqueous humor formation. The proposal to investigate endogenous neural and humoral regulating mechanisms is one of the N.E.I. glaucoma panels program development priorities.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY000237-24
Application #
3255205
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1977-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
24
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
Bausher, L P; Gregory, D S; Sears, M L (1989) Alpha 2-adrenergic and VIP receptors in rabbit ciliary processes interact. Curr Eye Res 8:47-54
Bausher, L; Sears, M (1987) The effect of hCG on cyclic AMP in rabbit ciliary processes. J Ocul Pharmacol 3:101-9
Bausher, L P; Gregory, D S; Sears, M L (1987) Interaction between alpha 2- and beta 2-adrenergic receptors in rabbit ciliary processes. Curr Eye Res 6:497-505
Elman, J; Caprioli, J; Sears, M et al. (1987) Chorionic gonadotropin decreases intraocular pressure and aqueous humor flow in rabbit eyes. Invest Ophthalmol Vis Sci 28:197-200
Simone, D A; Ngeow, J Y; Putterman, G J et al. (1987) Hyperalgesia to heat after intradermal injection of capsaicin. Brain Res 418:201-3
Simone, D A; Ngeow, J Y; Whitehouse, J et al. (1987) The magnitude and duration of itch produced by intracutaneous injections of histamine. Somatosens Res 5:81-92
Putterman, G J; Sears, M L; Bausher, L (1986) Intravitreal injection of purified human chorionic gonadotropin lowers IOP in rabbits. J Ocul Pharmacol 2:121-9
Sears, M L; Kondo, K (1986) Drug effects upon aqueous production. Trans Ophthalmol Soc U K 105 ( Pt 2):171-9
Sears, M L (1985) Regulation of aqueous flow by the adenylate cyclase receptor complex in the ciliary epithelium. Am J Ophthalmol 100:194-8
Putterman, G J; Davidson, J; Albert, J (1985) Lack of metabolism of timolol by ocular tissues. J Ocul Pharmacol 1:287-96

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