Development of a Two-Color Fluorescent Tracer Technique to Study Aqueous Outflow Patterns and Outflow Resistance in Human Eyes

2007 ◽  
Author(s):  
Steven J. Folz ◽  
Hiayan Gong ◽  
Darryl R. Overby
Keyword(s):  
Intraocular Pressure ◽  
Aqueous Humor ◽  
Tracer Technique ◽  
Outflow Resistance ◽  
Fluorescent Tracer ◽  
Aqueous Humor Outflow ◽  
Elevated Intraocular Pressure ◽  
Human Eyes ◽  
Outflow Pathway ◽  
Aqueous Outflow

Glaucoma is a leading cause of blindness, and elevated intraocular pressure (IOP) characteristic of glaucoma is caused by increased aqueous humor outflow resistance. Studies have localized the bulk of outflow resistance to particular regions along the outflow pathway — namely, the inner wall endothelium of Schlemm’s canal and its underlying juxtacanalicular tissue (JCT) [1] — but the hydrodynamic details of how aqueous humor flows through these tissues and how these tissues generate outflow resistance are not well understood.

scholarly journals S1P2 receptor regulation of sphingosine-1-phosphate effects on conventional outflow physiology

2011 ◽  
Vol 300 (5) ◽  
pp. C1164-C1171 ◽  
Author(s):  
Grant M. Sumida ◽  
W. Daniel Stamer
Keyword(s):  
Intraocular Pressure ◽  
Open Angle Glaucoma ◽  
Primary Cultures ◽  
Receptor Activation ◽  
Outflow Resistance ◽  
Outflow Facility ◽  
Aqueous Humor Outflow ◽  
Sphingosine 1 Phosphate ◽  
Mlc Phosphorylation ◽  
Human Eyes

Elevated intraocular pressure is the main risk factor in primary open-angle glaucoma, involving an increased resistance to aqueous humor outflow in the juxtacanalicular region of the conventional outflow pathway which includes the trabecular meshwork (TM) and the inner wall of Schlemm's canal (SC). Previously, sphingosine-1-phosphate (S1P) was shown to decrease outflow facility in porcine and human eyes, thus increasing outflow resistance and intraocular pressure. Owing to S1P's known effect of increasing barrier function in endothelial cells and the robust expression of the S1P1 receptor on the inner wall of SC, we hypothesized that S1P1 receptor activation promotes junction formation and decreases outflow facility. The effects of subtype-specific S1P receptor compounds were tested in human and porcine whole-eye perfusions and human primary cultures of SC and TM cells to determine the receptor responsible for S1P effects on outflow resistance. The S1P1-specific agonist SEW2871 failed to both mimic S1P effects in paired human eye perfusions, as well as increase myosin light chain (MLC) phosphorylation in cell culture, a prominent outcome in S1P-treated SC and TM cells. In contrast, the S1P2 antagonist JTE-013, but not the S1P1 or S1P1,3 antagonists, blocked the S1P-promoted increase in MLC phosphorylation. Moreover, JTE-013 prevented S1P-induced decrease in outflow facility in perfused human eyes ( P < 0.05, n = 6 pairs). Similarly, porcine eyes perfused with JTE-013 + S1P did not differ from eyes with JTE-013 alone ( P = 0.53, n = 3). These results demonstrate that S1P2, and not S1P1 or S1P3, receptor activation increases conventional outflow resistance and is a potential target to regulate intraocular pressure.

scholarly journals Imaging the aqueous humor outflow pathway in human eyes by three-dimensional micro-computed tomography (3D micro-CT)

2011 ◽  
Vol 92 (2) ◽  
pp. 104-111 ◽  
Author(s):  
Cheryl R. Hann ◽  
Michael D. Bentley ◽  
Andrew Vercnocke ◽  
Erik L. Ritman ◽  
Michael P. Fautsch
Keyword(s):  
Computed Tomography ◽  
Aqueous Humor ◽  
Three Dimensional ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Aqueous Humor Outflow ◽  
Human Eyes ◽  
Outflow Pathway

Trabecular Bypass: Effect of Schlemm’s Canal and Collector Channel Dilation

2004 ◽  
Author(s):  
Jianbo Zhou ◽  
Gregory T. Smedley
Keyword(s):  
Intraocular Pressure ◽  
Second Order ◽  
Polynomial Equations ◽  
Outflow Resistance ◽  
Schlemm’S Canal ◽  
Schlemm's Canal ◽  
Elevated Intraocular Pressure ◽  
Order Polynomial ◽  
Trabecular Bypass

An ocular outflow model is proposed to theorize the effect of Schlemm’s canal (SC) and/or collector channel (CC) dilation combined with a trabecular bypass on elevated intraocular pressure (IOP) in glaucomatous eyes. The dilated height of the elliptic SC is largest at the bypass and linearly deceases to the non-dilated height over the dilated circumferential length. The CC dilation is modeled with a reduced outflow resistance of second order polynomial. Equations governing the pressure and flow in SC are solved numerically. The model predicts that the IOP is reduced substantially with moderate dilation from the normal 20 μm to 40 μm at the bypass. SC dilation is more effective for eyes with smaller SC. The dilation of CC can also significantly lower the IOP. With the trabecular bypass alone, the elevated IOP is expected to drop to the mid-to-high teens. The IOP can be further reduced by another 3 to 6 mmHg with moderate SC and CC dilation.

scholarly journals Individual molecular response to elevated intraocular pressure in perfused postmortem human eyes

2009 ◽  
Vol 38 (2) ◽  
pp. 205-225 ◽  
Author(s):  
Núria Comes ◽  
Teresa Borrás
Keyword(s):  
Intraocular Pressure ◽  
Trabecular Meshwork ◽  
Elevated Pressure ◽  
Individual Response ◽  
Molecular Response ◽  
Affymetrix Genechips ◽  
Elevated Intraocular Pressure ◽  
Taqman Pcr ◽  
The Individual ◽  
Human Eyes

Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. In the clinic, the response to elevated pressure and thus the risk for development of glaucoma differs among individuals. We took advantage of our ability to subject postmortem human eyes from the same individual to physiological and elevated pressure in a perfused outflow model and compared individual patterns of gene expression under pressure. The architecture of the trabecular meshwork, tissue responsible for the maintenance of IOP, was conserved. We performed two sets of experiments. The first set ( n = 5, 10 eyes) used Affymetrix GeneChips, identified the 20 most pressure-altered genes in each individual, and compared their pressure response in the other four. The second set ( n = 5, 10 eyes) selected 21 relevant trabecular meshwork genes and examined, by real-time TaqMan-PCR, the rank of their abundance and of their pressure differential expression in each individual. The majority of the up- and downregulated top-changers of each individual showed an individual response trend. Few genes were general responders. Individual responders included STATH, FBN2, TF, OGN, IL6, IGF1, CRYAB, and ELAM1 (marker for glaucoma). General responders included MMP1, MMP10, CXCL2, and PDPN. In addition, we found that although the relative abundance of selected genes was very similar among nonstressed individuals, the response to pressure of those same genes had a marked individual component. Our results offer the first molecular insight on the variation of the individual response to IOP observed in the clinical setting.

Sign in / Sign up

Export Citation Format

Share Document