The pore density in the inner wall endothelium of Schlemm's canal of glaucomatous eyes

Mark Johnson, Darren Chan, A. Thomas Read, Cindy Christensen, Arthur J Sit, C. Ross Ethier

Research output: Contribution to journalArticle

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Abstract

PURPOSE. In a prior study, it has been reported that glaucomatous eyes have a significantly lower density of pores in the inner wall of Schlemm's canal than do normal eyes. However, in that study the glaucomatous eyes were fixed at much lower flow rates than the normal eyes, and that is now known to affect inner wall pore density. The objective of the current study was to compare the inner wall's pore density in glaucomatous and normal eyes, accounting for the effects of fixation conditions. METHODS. Outflow facility was measured in enucleated glaucomatous human eyes. Eyes were fixed under constant flow conditions, microdissected to expose the inner wall of Schlemm's canal, and prepared for scanning electron microscopy (SEM). The density and diameter of the two subpopulations of pores in the inner wall, intracellular and intercellular (or "border") pores, were measured. Data were compared with those in previous studies of normal eyes. RESULTS. As previously, reported, pore density decreased with increasing postmortem time and increased with increasing volume of fixative passed through the outflow pathway and with increasing fixation time. Linear regression analysis indicated that glaucomatous eyes had less than one fifth the number of pores than normal eyes have, after accounting for the influence of volume of fixative perfused through the eyes (835 pores/mm2 in normal eyes versus 160 pores/mm2 in glaucomatous eyes). A nonlinear regression of pore density versus fixative volume produced a pore density at zero fixative volume that was not statistically different from zero. If true, this implies that all (or nearly all) inner wall pores observed by SEM are fixation artifacts. The density of intracellular pores and the diameter of these pores correlated with the density and diameter of the border pores, respectively. CONCLUSIONS. Inner wall pores are reduced in glaucomatous eyes. If pores are physiological structures, the elevated intraocular pressure characteristic of glaucoma may be explained by decreased porosity of the inner wall endothelium. Both border and intracellular pores seem to be induced in a similar fashion by fixation. The unlikely possibility that all inner wall pores are fixation-induced cannot be excluded. If so, a fundamental reassessment of the mechanism by which aqueous humor crosses the inner wall endothelium is necessary.

Original languageEnglish (US)
Pages (from-to)2950-2955
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number9
StatePublished - Sep 2002
Externally publishedYes

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Endothelium
Fixatives
Electron Scanning Microscopy
Aqueous Humor
Porosity
Intraocular Pressure
Glaucoma
Artifacts
Linear Models
Regression Analysis

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Johnson, M., Chan, D., Read, A. T., Christensen, C., Sit, A. J., & Ethier, C. R. (2002). The pore density in the inner wall endothelium of Schlemm's canal of glaucomatous eyes. Investigative Ophthalmology and Visual Science, 43(9), 2950-2955.

The pore density in the inner wall endothelium of Schlemm's canal of glaucomatous eyes. / Johnson, Mark; Chan, Darren; Read, A. Thomas; Christensen, Cindy; Sit, Arthur J; Ethier, C. Ross.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 9, 09.2002, p. 2950-2955.

Research output: Contribution to journalArticle

Johnson, M, Chan, D, Read, AT, Christensen, C, Sit, AJ & Ethier, CR 2002, 'The pore density in the inner wall endothelium of Schlemm's canal of glaucomatous eyes', Investigative Ophthalmology and Visual Science, vol. 43, no. 9, pp. 2950-2955.
Johnson, Mark ; Chan, Darren ; Read, A. Thomas ; Christensen, Cindy ; Sit, Arthur J ; Ethier, C. Ross. / The pore density in the inner wall endothelium of Schlemm's canal of glaucomatous eyes. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 9. pp. 2950-2955.
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N2 - PURPOSE. In a prior study, it has been reported that glaucomatous eyes have a significantly lower density of pores in the inner wall of Schlemm's canal than do normal eyes. However, in that study the glaucomatous eyes were fixed at much lower flow rates than the normal eyes, and that is now known to affect inner wall pore density. The objective of the current study was to compare the inner wall's pore density in glaucomatous and normal eyes, accounting for the effects of fixation conditions. METHODS. Outflow facility was measured in enucleated glaucomatous human eyes. Eyes were fixed under constant flow conditions, microdissected to expose the inner wall of Schlemm's canal, and prepared for scanning electron microscopy (SEM). The density and diameter of the two subpopulations of pores in the inner wall, intracellular and intercellular (or "border") pores, were measured. Data were compared with those in previous studies of normal eyes. RESULTS. As previously, reported, pore density decreased with increasing postmortem time and increased with increasing volume of fixative passed through the outflow pathway and with increasing fixation time. Linear regression analysis indicated that glaucomatous eyes had less than one fifth the number of pores than normal eyes have, after accounting for the influence of volume of fixative perfused through the eyes (835 pores/mm2 in normal eyes versus 160 pores/mm2 in glaucomatous eyes). A nonlinear regression of pore density versus fixative volume produced a pore density at zero fixative volume that was not statistically different from zero. If true, this implies that all (or nearly all) inner wall pores observed by SEM are fixation artifacts. The density of intracellular pores and the diameter of these pores correlated with the density and diameter of the border pores, respectively. CONCLUSIONS. Inner wall pores are reduced in glaucomatous eyes. If pores are physiological structures, the elevated intraocular pressure characteristic of glaucoma may be explained by decreased porosity of the inner wall endothelium. Both border and intracellular pores seem to be induced in a similar fashion by fixation. The unlikely possibility that all inner wall pores are fixation-induced cannot be excluded. If so, a fundamental reassessment of the mechanism by which aqueous humor crosses the inner wall endothelium is necessary.

AB - PURPOSE. In a prior study, it has been reported that glaucomatous eyes have a significantly lower density of pores in the inner wall of Schlemm's canal than do normal eyes. However, in that study the glaucomatous eyes were fixed at much lower flow rates than the normal eyes, and that is now known to affect inner wall pore density. The objective of the current study was to compare the inner wall's pore density in glaucomatous and normal eyes, accounting for the effects of fixation conditions. METHODS. Outflow facility was measured in enucleated glaucomatous human eyes. Eyes were fixed under constant flow conditions, microdissected to expose the inner wall of Schlemm's canal, and prepared for scanning electron microscopy (SEM). The density and diameter of the two subpopulations of pores in the inner wall, intracellular and intercellular (or "border") pores, were measured. Data were compared with those in previous studies of normal eyes. RESULTS. As previously, reported, pore density decreased with increasing postmortem time and increased with increasing volume of fixative passed through the outflow pathway and with increasing fixation time. Linear regression analysis indicated that glaucomatous eyes had less than one fifth the number of pores than normal eyes have, after accounting for the influence of volume of fixative perfused through the eyes (835 pores/mm2 in normal eyes versus 160 pores/mm2 in glaucomatous eyes). A nonlinear regression of pore density versus fixative volume produced a pore density at zero fixative volume that was not statistically different from zero. If true, this implies that all (or nearly all) inner wall pores observed by SEM are fixation artifacts. The density of intracellular pores and the diameter of these pores correlated with the density and diameter of the border pores, respectively. CONCLUSIONS. Inner wall pores are reduced in glaucomatous eyes. If pores are physiological structures, the elevated intraocular pressure characteristic of glaucoma may be explained by decreased porosity of the inner wall endothelium. Both border and intracellular pores seem to be induced in a similar fashion by fixation. The unlikely possibility that all inner wall pores are fixation-induced cannot be excluded. If so, a fundamental reassessment of the mechanism by which aqueous humor crosses the inner wall endothelium is necessary.

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