Is a key controller of intraocular pressure regulated?

Jeffrey Kiel, PhD
The University of Texas Health Science Center at San Antonio (San Antonio, TX)
Year Awarded:
2010
Grant Duration:
April 1, 2010 to March 31, 2012
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2010032
Award Type:
Standard
Award Region:
US Southern
Jeffrey Kiel, PhD

Regulation of episcleral venuos pressure

Summary

Episcleral venous pressure (EVP) is a primary cause of intraocular pressure (IOP), yet we know little about it. The episcleral blood vessels have nerves, which suggests that EVP is regulated, but we do not know if failure of EVP regulation causes high IOP, or if we can lower EVP with drugs as a new way to treat glaucoma. This project seeks to shed light on the answers to these questions.

Details

High intraocular pressure (IOP) is the main risk factor for glaucoma and lowering IOP is the primary treatment. Episcleral venous pressure (EVP), the pressure of the blood vessels in the sclera, or 'whites' of the eye, is a main determinant of IOP; yet we know little about it, and very few studies address the subject. The episcleral blood vessels have lots of nerves, which suggests that EVP is regulated. We do not know if failure of EVP regulation causes high IOP, or if we can lower EVP with drugs as a new way to treat glaucoma. This project seeks to find out. Our results will provide new insight into a cause of glaucoma and provide a new target for drugs to treat the disease. We will use a new technique to measure EVP and see how EVP changes as test subjects move from sitting to laying down. We will use a new technology to study EVP that overcomes the major limitation of the 'venomanometry' method used in most prior studies. In venomanometry, a topical anesthetic is applied for subject comfort. Topical anesthesia eliminates any chance of studying neural control of EVP, and so this neural control has not been studied before. These studies will identify the nerves that protect the EVP from changes in cerebral venous pressure that occur due to changes in body position. The results of this study may pave the way for development of new therapies designed to lower IOP through regulation of EVP.

Research Updates

This project focused on the way the intraocular pressure, or "IOP" reacts to changes in posture. When humans lay down, the IOP rises, but much less than it should. Dr. Kiel’s team suspected this is because the pressure in the veins just outside the eye is tightly regulated. This episcleral venous pressure, or "EVP," is difficult to measure in humans, and so they studied it in an animal model. In the past two years, the team has confirmed that the IOP is protected in their animals as it is in humans when they lay down, and that this is not due to decreased aqueous production. Instead, the team found that when they simulate lying down in their animals, the venous pressure and the IOP increase by a similar, small amount that is significantly less than expected. They suspect the EVP is controlled by a neural reflex, but their tests so far indicate that the sympathetic and parasympathetic nerves (components of the autonomic nervous system) are not involved. They have also tested other possible nerves and local mechanisms that might be responsible, and have found that some of them may be responsible. What makes this work potentially important is that humans spend roughly a third of their lives lying down. If there is a neural reflex that controls EVP and so protects IOP, what if it fails? Does this cause the IOP to go up too high when someone lays down and so contribute to glaucoma? Or can drugs mimic the reflex to decrease EVP and provide a new way to lower IOP and treat glaucoma? Dr. Kiel’s team will continue studying EVP with NIH support in order to find out.

Publications

Magnetic resonance imaging of vascular oxygenation changes during hyperoxia and carbogen challenges in the human retina. Zhang Y, Peng Q, Kiel JW, Rosende CA, Duong TQ. Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):286-91. Print 2011 Jan. PubMed Icon Google Scholar Icon

Venous Pressure and Intraocular Pressure Homeostasis. Ph.D. Dissertation, W.J. Lavery, University of Texas Health Science Center at San Antonio, San Antonio, TX. 2012.

Lavery WJ, Kiel JW. Effects of head down tilt on episcleral venous pressure in a rabbit model. Exp Eye Res. 2013 Apr 6. doi:pii: S0014-4835(13)00080-8. 10.1016/j.exer.2013.03.020. [Epub ahead of print] PubMed Icon Google Scholar Icon

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