Glaucoma, a leading cause of blindness in the United States, is associated with an increased intraocular pressure (IOP) that results from an increased resistance to the flow of aqueous humor as it drains from the eye. However, the source of this increased flow resistance has not been determined. Our overall goals are to determine (i) how flow resistance is generated in the normal eye, (ii) how this flow resistance is modulated and (iii) what causes this flow resistance to increase in glaucoma. It is conventionally believed that the juxtacanalicular tissue (JCT), immediately underlying Schlemm's canal, is responsible for the bulk of outflow resistance in the normal eye, and that changes in the extracellular matrix in this region lead to glaucoma. Our group has now shown that the JCT, as visualized using a morphological technique known as quick-freeze/deep-etch, cannot generate a significant fraction of outflow resistance, at least in the normal human eye. This is an important conclusion, and we propose to continue to use this technique to examine the glaucomatous eye. The endothelium forming the inner wall of Schlemm's canal is widely thought to generate only a small fraction of outflow resistance, based on a hydrodynamic assessment of endothelial pores in the inner wall. However, we have recently demonstrated that the pore density in glaucomatous eyes is less than that found in normal eyes, perhaps as much as five-fold less. This suggests that the elevated flow resistance of glaucomatous eyes may be due to a decreased capacity to form these endothelial pores. We will examine this possibility in our proposed studies. If confirmed, these findings may finally allow us to find the ultimate cause of the elevated IOP characteristic of glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009699-10
Application #
6864419
Study Section
Special Emphasis Panel (ZRG1-VISA (01))
Program Officer
Liberman, Ellen S
Project Start
1993-03-01
Project End
2008-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
10
Fiscal Year
2005
Total Cost
$435,219
Indirect Cost
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Vargas-Pinto, Rocio; Lai, Julia; Gong, Haiyan et al. (2015) Finite element analysis of the pressure-induced deformation of Schlemm's canal endothelial cells. Biomech Model Mechanobiol 14:851-63
Freddo, Thomas F (2013) A contemporary concept of the blood-aqueous barrier. Prog Retin Eye Res 32:181-95
Zeng, Dehong; Juzkiw, Taras; Read, A Thomas et al. (2010) Young's modulus of elasticity of Schlemm's canal endothelial cells. Biomech Model Mechanobiol 9:19-33
Johnson, Mark; Caro, Nathan; Huang, Jiahn-Dar (2010) Adequacy of exchanging the content of the anterior chamber. Exp Eye Res 91:876-80
Overby, Darryl R; Stamer, W Daniel; Johnson, Mark (2009) The changing paradigm of outflow resistance generation: towards synergistic models of the JCT and inner wall endothelium. Exp Eye Res 88:656-70
Gong, Haiyan; Freddo, Thomas F (2009) The washout phenomenon in aqueous outflow--why does it matter? Exp Eye Res 88:729-37
Freddo, Thomas F; Gong, Haiyan (2009) ETIOLOGY OF IOP ELEVATION IN PRIMARY OPEN ANGLE GLAUCOMA. Optom Glaucoma Soc E J 4:
Lu, Zhaozeng; Overby, Darryl R; Scott, Patrick A et al. (2008) The mechanism of increasing outflow facility by rho-kinase inhibition with Y-27632 in bovine eyes. Exp Eye Res 86:271-81
Scott, Patrick A; Overby, Darryl R; Freddo, Thomas F et al. (2007) Comparative studies between species that do and do not exhibit the washout effect. Exp Eye Res 84:435-43
Johnson, Mark (2006) 'What controls aqueous humour outflow resistance?'. Exp Eye Res 82:545-57

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