Effect of hydrostatic pressure gradients and Na<sub>2</sub>EDTA on permeability of human Schlemm's canal cell monolayers

Burke, A.G.; Zhou, Wentao; Roberts, Bruce C.; Stamer, W. Daniel

doi:10.1080/02713680490503697

Cited by 17 publications

(13 citation statements)

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“…Ethier and Chan (Ethier and Chan, 2001) found that cationized ferritin perfused into enucleated human eyes acted to decreased outflow facility and was seen accumulating near junctions between inner wall endothelial cells. While Ethier and Chan argue that the decreased outflow facility caused by cationized ferritin was due to pore blocking that was also seen to occur in this study, others (Burke et al, 2004) have interpreted their results as consistent with a significant flow through the junctional complexes.…”

Section: Pores As Possible Fixation Artifacts and The Possible Importsupporting

confidence: 57%

“…These studies have shown that the permeability to solutes, electrical resistance, and hydraulic conductivity can continue to change one to 2 weeks post confluence in endothelial monolayers. Measurements of hydraulic conductivity should only be made after the junctions become stable (Burke et al, 2004). This is especially a concern for studies using steroids or other agents that directly affect these junctions and thus can influence how long they take to become stable (Underwood et al, 1999).…”

Section: Future Workmentioning

confidence: 99%

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‘What controls aqueous humour outflow resistance?’

Johnson

2006

Experimental Eye Research

405

366

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The bulk of aqueous humour outflow resistance is generated in or near the inner wall endothelium of Schlemm's canal in normal eyes, and probably also in glaucomatous eyes. Fluid flow through this region is controlled by the location of the giant vacuoles and pores found in cells of the endothelium of Schlemm's canal, but the flow resistance itself is more likely generated either in the extracellular matrix of the juxtacanalicular connective tissue or the basement membrane of Schlemm's canal. Future studies utilizing in vitro perfusion studies of inner wall endothelial cells may give insights into the process by which vacuoles and pores form in this unique endothelium and why inner wall pore density is greatly reduced in glaucoma. Keywordsglaucoma; Schlemm's canal; hydraulic conductivity It has been recognized for more that 130 years that the elevated pressure characteristic of primary open-angle glaucoma arises due to an increased resistance to the outflow of aqueous humour from the eye. (Leber, 1873) However, a conclusive determination of where in the outflow pathways this elevated outflow resistance is generated has been elusive. Surprisingly, the locus of aqueous humour outflow resistance in the normal eye has also been not been unequivocally determined.Seidel (1921) using light microscopy, stated 'that the inner wall of Schlemm's canal stand in open communication with the anterior chamber, and that the aqueous humour directly washes around the inner wall endothelium of Schlemm's canal and is only separated from the lumen of Schlemm's canal by a thin, outer membrane'. Our view is little different today. The locus of outflow resistance, both in the normal eye and the glaucomatous eye, is thought to arise either in the endothelial lining of Schlemm's canal, or very near to this location. In this article, current thoughts on where that flow resistance might be generated are reviewed.There are a number of excellent review articles (Tripathi, 1974a,b;Bill, 1975;Bill and Mäepea, 1994;Gong et al., 1996;Johnson and Erickson, 2000;Ethier, 2002) that describe the detailed morphology and physiology of the aqueous outflow pathway. In this review, the evidence that leads to the conclusion that the inner wall region is responsible for the bulk of aqueous humour outflow resistance is first presented. Then, attention is focused on those proximal aspects of this pathway that are nearest to the endothelial linings of Schlemm's canal, and the transport characteristics of these structures.The bulk of the aqueous humour flows out of the anterior chamber of the eye through the conventional aqueous outflow pathway comprised of the trabecular meshwork, the juxtacanalicular connective tissue, the endothelial lining of Schlemm's canal, Schlemm's canal itself, the collecting channels and aqueous veins, and then finally drains into the episcleral NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript venous system, rejoining the blood from whence it came (in this review, the juxtacanalicular...

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Section: Pores As Possible Fixation Artifacts and The Possible Importsupporting

confidence: 57%

Section: Future Workmentioning

confidence: 99%

‘What controls aqueous humour outflow resistance?’

Johnson

2006

Experimental Eye Research

405

366

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“…Concerning the study of glaucoma, EHP has been used to mimic ocular hypertension. Several studies have reported the effect of EHP on cells of the trabecular meshwork [18][19][20] and Schlemm's canal [21] and other cell types [22] . The mechanisms whereby retinal cells sense mechanical pressure have not yet been completely elucidated, yet some possibilities have been considered [for a review, see 23 ].…”

Section: Advantages Of Using In Vitro Models To Study Glaucomamentioning

confidence: 99%

Modeling Human Glaucoma: Lessons from the in vitro Models

Aires

Ambrósio²,

Santiago³

2016

Ophthalmic Res

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Glaucoma, a leading cause of blindness worldwide, is a degenerative disease characterized by retinal ganglion cell (RGC) loss and optic nerve atrophy. Elevated intraocular pressure (IOP) is a main risk factor for onset and progression of the disease. Since increased IOP is the only modifiable risk factor, relevant models for glaucoma would comprise RGC and optic nerve damage triggered by ocular hypertension. Animal models of glaucoma have greatly contributed to the understanding of the molecular mechanisms of this pathology, and they have also facilitated the development of new pharmacological interventions. Although animal models of glaucoma have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. There is a recognized demand for in vitro models that can replace or reduce the need for animal experiments. Several in vitro models have emerged as a great opportunity in the field of glaucoma research, helping to clarify the mechanisms involved in disease progression. Several types of equipment have been developed to expose cells and tissue cultures to elevated pressures. Herein, we discuss the methodology used to increase pressure, the main findings, and the relevance of in vitro models for the study of the pathophysiology of glaucoma.

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“…71,95,119 Inner wall of Schlemm's Canal Endothelia Different groups have isolated and characterized SCECs trying to asses its role in resistance to drainage, but its exact in vivo behavior still remains unclear. [120][121][122][123] Fluid transport across this monolayer does not resemble the typical flow observed across other blood vascular endothelium. In Schlemm's canal, the basal-to-apical directionality of flow pushes the ECs away from their basement membrane, resembling the flow across the lymphatic endothelium.…”

Section: Lymphatic Endotheliamentioning

confidence: 99%

“…Similar to the way lymphatic capillaries respond to strain or pressure gradients by opening interendothelial clefts via anchoring filaments; the inner wall of Schlemm's canal responds to changes in IOP by reducing complexity of intracellular junctions, and decreasing EC overlap. 9,120 The exact route that the aqueous humor follows to exit the conventional pathway has been, for several years, a matter of debate. Two complementary theories, transcellular and paracellular pathways, have been proposed describing aqueous humor outflow; however, the exact contribution of each one of these pathways still remains uncertain.…”

Section: Lymphatic Endotheliamentioning

confidence: 99%

Schlemm??s Canal Endothelia, Lymphatic, or Blood Vasculature?

Ramos

Hoying

Witte

et al. 2007

Journal of Glaucoma

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In the human eye, the final barrier for aqueous humor to cross before returning to systemic circulation is the inner wall of Schlemm's canal. Unfortunately, the specific contribution of the inner wall to total outflow resistance in the conventional pathway is unknown in both normal and glaucomatous eyes. To better understand inner wall physiology, we contrasted it with 2 specialized continuous endothelia, initial lymphatic, and blood capillary endothelia. Specifically, we compare their developmental origin, morphology, junctional complexes, microenvironment, and physiologic responses to different biomechanical factors. Our evaluation concludes that the inner wall of Schlemm's canal is unique, sharing extraordinary characteristics with both types of specialized endothelia in addition to having distinctive features of its own.

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Effect of hydrostatic pressure gradients and Na₂EDTA on permeability of human Schlemm's canal cell monolayers

Abstract: Responses of Schlemm's Canal cells to pressure and calcium chelators in vitro are consistent with a role for calcium sensitive junctions in outflow resistance in vivo.

Cited by 17 publications

References 11 publications

‘What controls aqueous humour outflow resistance?’

‘What controls aqueous humour outflow resistance?’

Modeling Human Glaucoma: Lessons from the in vitro Models

Schlemm??s Canal Endothelia, Lymphatic, or Blood Vasculature?

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Effect of hydrostatic pressure gradients and Na2EDTA on permeability of human Schlemm's canal cell monolayers

Abstract: Responses of Schlemm's Canal cells to pressure and calcium chelators in vitro are consistent with a role for calcium sensitive junctions in outflow resistance in vivo.

Cited by 17 publications

References 11 publications

‘What controls aqueous humour outflow resistance?’

‘What controls aqueous humour outflow resistance?’

Modeling Human Glaucoma: Lessons from the in vitro Models

Schlemm??s Canal Endothelia, Lymphatic, or Blood Vasculature?

Contact Info

Product

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Effect of hydrostatic pressure gradients and Na₂EDTA on permeability of human Schlemm's canal cell monolayers