Open-angle glaucoma is associated with an elevated intraocular pressure (IOP) resulting from the disturbance of normal aqueous humor dynamics. Clinical observations indicate that aqueous humor dynamics is regulated to some extent by the central nervous system (CNS through neural and hormonal pathways. However, laboratory data about such actions were either lacking or inconsistent. This project incorporates advanced technology to systematically investigate endogenous neural and hormonal mechanisms in the regulation of aqueous humor dynamics, using the rabbit as a model. Several physiological actions that have profound effects on IOP in conscious rabbits have been identified. Their signal transductions in vivo will be studied in three experimental conditions: circadian change of IOP (Aim 1), electric stimulation o the cervical sympathetic nerves (Aim 2), and endogenous elevation of circulating catecholamines by intravenous injection of thyrotropin releasing hormone (Aim 3). The ocular neurotransmitters and intracellular second messengers (cyclic AMP, diacylglycerol, and inositol 1,4, 5 trisphosphate) mediating the responses will be identified and quantified. Laser irradiation will be use to halt the degradation of intracellular second messengers. Fluorophotometry will be used to measure aqueous flow. The role of the paraventricular nucleus (Aim 4) and the suprachiasmatic nucleus (Aim 5) in the regulation of aqueous humor dynamics in conscious rabbits will be studied by ablation and electric stimulation of these nuclei. CNS neural circuit and efferent pathways will be determined. The interactions between the pituitary hormonal axes and the endogenous mechanisms affecting aqueous humor dynamics (Aim 6) will be clarified after the hormonal axes are activated by administration of pituitary hormone releasing factors: luteinizing hormone releasing hormone, corticotropin releasing factor, and growth hormone releasing hormone. This project will reveal fundamental neural and hormonal mechanisms in the endogenous regulation of aqueous humor dynamics in rabbits. This new knowledge should benefit relevant research in other species and help to refine the rationale for developing more effective antiglaucoma treatment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007544-06
Application #
3264514
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1991-11-01
Project End
1996-02-29
Budget Start
1992-03-01
Budget End
1993-02-28
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Grippo, Tomas M; Liu, John H K; Zebardast, Nazlee et al. (2013) Twenty-four-hour pattern of intraocular pressure in untreated patients with ocular hypertension. Invest Ophthalmol Vis Sci 54:512-7
Loewen, Nils A; Liu, John H K; Weinreb, Robert N (2010) Increased 24-hour variation of human intraocular pressure with short axial length. Invest Ophthalmol Vis Sci 51:933-7
Deokule, Sunil P; Doshi, Amish; Vizzeri, Gianmarco et al. (2009) Relationship of the 24-hour pattern of intraocular pressure with optic disc appearance in primary open-angle glaucoma. Ophthalmology 116:833-9
Valderrama, Chad M; Li, Ruixia; Liu, John H K (2008) Direct effect of light on 24-h variation of aqueous humor protein concentration in Sprague-Dawley rats. Exp Eye Res 87:487-91
Kida, Teruyo; Liu, John H K; Weinreb, Robert N (2008) Effect of aging on nocturnal blood flow in the optic nerve head and macula in healthy human eyes. J Glaucoma 17:366-71
Kida, Teruyo; Liu, John H K; Weinreb, Robert N (2008) Effects of aging on corneal biomechanical properties and their impact on 24-hour measurement of intraocular pressure. Am J Ophthalmol 146:567-572
Li, Ruixia; Liu, John H K (2008) Telemetric monitoring of 24 h intraocular pressure in conscious and freely moving C57BL/6J and CBA/CaJ mice. Mol Vis 14:745-9
Liu, John H K; Li, Ruixia; Nelson, Thomas R et al. (2007) Sympathetic activities influence blood-flow velocity and resistance in the rabbit ophthalmic artery. J Ocul Pharmacol Ther 23:110-5
Liu, John H K; Li, Ruixia; Nelson, Thomas R et al. (2007) Resistance to blood flow in the rabbit ophthalmic artery after topical treatment with timolol. J Ocul Pharmacol Ther 23:103-9
Lee, Alexander C; Mosaed, Sameh; Weinreb, Robert N et al. (2007) Effect of laser trabeculoplasty on nocturnal intraocular pressure in medically treated glaucoma patients. Ophthalmology 114:666-70

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