The objectives of this proposal are to study neural and pharmacological controls of aqueous humor dynamics. Neural mechanisms will investigate the ocular effects of neuropeptides (pancreatic polypeptide, vasoactive intestinal polypeptide, etc.) and physiological regulators of aqueous humor dynamics. These agents will be studied via peripheral (topical, intracameral, intravitreal) and central (third ventricle and hypothalamic microinjection) routes of administration. Neural pathways are to be investigated by ablation of the superior cervical ganglion, greater superficial petrosal nerve and trigeminal nerve. Pharmacological controls will study ocular carbonic anhydrase with special attention to topically active inhibitory agents; the intraocular pressure lowering effect of topical dopamine as well as the effect of specific dopamine receptor (DA1 and DA2) agonists and antagonists; and the intraocular pressure effect of topical cannabinoid compounds. Aqueous humor dynamics will include intraocular pressure, outflow facility, episcleral venous pressure, aqueous humor flow, and ocular blood flow and volume. These studies relate to the regulation of intraocular pressure. The results will provide information on the role of neuropeptides as physiological regulators of aqueous humor dynamics and may provide clues about the underlying pathophysiology of glaucoma. Pharmacological modulation of intraocular pressure will provide insight into normal aqueous humor physiology and possibly new glaucoma therapeutic agents.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005267-02
Application #
3260231
Study Section
(SSS)
Project Start
1984-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Presbyterian Medical Center of Phila
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Wallace, I; Krupin, T; Stone, R A et al. (1989) The ocular hypotensive effects of demeclocycline, tetracycline and other tetracycline derivatives. Invest Ophthalmol Vis Sci 30:1594-8
Wallace, I; Moolchandani, J; Krupin, T et al. (1988) Effects of systemic desmopressin on aqueous humor dynamics in rabbits. Invest Ophthalmol Vis Sci 29:406-10
Piccone, M; Littzi, J; Krupin, T et al. (1988) Effects of neuropeptide Y on the isolated rabbit iris dilator muscle. Invest Ophthalmol Vis Sci 29:330-2
Moolchandani, J; Krupin, T (1987) Central effects of vasoactive intestinal polypeptide on intraocular pressure and body temperature in rabbits. Curr Eye Res 6:935-41
Krupin, T; Wax, M; Moolchandani, J (1986) Aqueous production. Trans Ophthalmol Soc U K 105 ( Pt 2):156-61
Krupin, T; Fritz, C; Becker, B (1985) Maturation of Rb+ and PAH accumulation by rabbit anterior uvea and choroid plexus. Invest Ophthalmol Vis Sci 26:159-62
Krupin, T; Sly, W S; Whyte, M P et al. (1985) Failure of acetazolamide to decrease intraocular pressure in patients with carbonic anhydrase II deficiency. Am J Ophthalmol 99:396-9