The project's broad goal is to define the roles of ocular blood flow in intraocular pressure (IOP) homeostasis and incorporate that information into a mathematical model of ocular hydrodynamics. The project's goal for this cycle is to increase our knowledge of episcleral venous pressure (EVP) and its regulation. This is important for two reasons. First, EVP is the pressure that aqueous must overcome to leave the eye via the trabecular outflow pathway, which makes it a principle factor in aqueous dynamics and IOP homeostasis. However, EVP is difficult to measure, so we know little about it and generally assume it is relatively stable. Given that the episcleral circulation is innervated and that most published EVP measurements were made under local anesthesia, that assumption is probably wrong. Rather, preliminary data obtained with a new technique show EVP is dynamic and regulated, and that fact will change our understanding of aqueous dynamics. Second, EVP is a heretofore unexplored target for lowering IOP in glaucoma patients, even though it has the potential to lower IOP significantly without the need for intraocular drug penetration. The next cycle has three specific aims: 1) translate our established rabbit model to a rat model for studying EVP (the rat outflow system is more similar to humans), 2) determine baseline values for relevant systemic and ocular parameters in the rat model, and 3) determine the neurotransmitters and receptors controlling EVP. The proposed research will increase our knowledge of the episcleral circulation and its role in aqueous dynamics, and reveal its potential as a new therapeutic approach for lowering IOP in glaucoma patients.

Public Health Relevance

The project's goal is to increase our knowledge of episcleral venous pressure (EVP) and how it sets intraocular pressure (IOP), the primary risk factor and treatment target for glaucoma. EVP is difficult to measure, so we know little about it and generally assume it is constant;however, results obtained with a new technique show EVP is dynamic and regulated, and that lowering EVP lowers IOP significantly without the need for intraocular drug penetration. EVP is not now a target for glaucoma drugs, but it should be.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009702-17
Application #
8249023
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Chin, Hemin R
Project Start
1992-08-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
17
Fiscal Year
2012
Total Cost
$372,708
Indirect Cost
$122,708
Name
University of Texas Health Science Center San Antonio
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Bogner, Barbara; Runge, Christian; Strohmaier, Clemens et al. (2014) The effect of vasopressin on ciliary blood flow and aqueous flow. Invest Ophthalmol Vis Sci 55:396-403
Li, Guang; Kiel, Jeffrey W; Cardenas, Damon P et al. (2013) Postocclusive reactive hyperemia occurs in the rat retinal circulation but not in the choroid. Invest Ophthalmol Vis Sci 54:5123-31
Strohmaier, Clemens A; Reitsamer, Herbert A; Kiel, Jeffrey W (2013) Episcleral venous pressure and IOP responses to central electrical stimulation in the rat. Invest Ophthalmol Vis Sci 54:6860-6
Li, Guang; Shih, Yen-Yu Ian; Kiel, Jeffrey W et al. (2013) MRI study of cerebral, retinal and choroidal blood flow responses to acute hypertension. Exp Eye Res 112:118-24
Shih, Yen-Yu I; Wang, Lin; De La Garza, Bryan H et al. (2013) Quantitative retinal and choroidal blood flow during light, dark adaptation and flicker light stimulation in rats using fluorescent microspheres. Curr Eye Res 38:292-8
Lavery, W J; Kiel, J W (2013) Effects of head down tilt on episcleral venous pressure in a rabbit model. Exp Eye Res 111:88-94
Lavery, William J; Muir, Eric R; Kiel, Jeffrey W et al. (2012) Magnetic resonance imaging indicates decreased choroidal and retinal blood flow in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci 53:560-4
De La Garza, Bryan H; Muir, Eric R; Shih, Yen-Yu I et al. (2012) 3D magnetic resonance microscopy of the ex vivo retina. Magn Reson Med 67:1154-8
Strohmaier, C; Werkmeister, R M; Bogner, B et al. (2011) A novel, microscope based, non-invasive laser Doppler flowmeter for choroidal blood flow assessment. Exp Eye Res 92:545-51
Kiel, J W; Hollingsworth, M; Rao, R et al. (2011) Ciliary blood flow and aqueous humor production. Prog Retin Eye Res 30:1-17

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