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Mark Johnson

Publications and source records attributed to Mark Johnson.

26 records · Page 2Linked to original sources
PubMed2002

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

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/mm(2) in normal eyes versus 160 pores/mm(2) 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.

Aged↗
PubMed2002

A new view of the human trabecular meshwork using quick-freeze, deep-etch electron microscopy.

Conventional transmission electron microscopic (TEM) images of the juxtacanalicular tissue (JCT) region of the trabecular meshwork (TM) show flow passages that are much too large to generate significant outflow resistance. The goal of the current study was to use quick-freeze/deep-etch (QF/DE), a technique that better preserves extracellular matrices, to determine if extracellular matrix material fills all the apparently 'open-spaces' that were observed using conventional TEM. Normal adult human eyes were fixed by immersion or under flow at pressures of 15 or 45 mmHg. The TM and the inner wall of Schlemm's canal (SC) were examined using QF/DE and compared to the observations using conventional TEM. The structure of the TM, as seen using QF/DE, showed much greater three dimensional ultrastructural detail than was seen with conventional TEM. Open space was confirmed to be present between the trabecular beams. Although significantly more extracellular matrix was observed in the JCT region using QF/DE than by conventional TEM, some micron-sized open-spaces were still present immediately beneath the inner wall of SC. Consistent with prior reports, the basement membrane of the cells lining the inner wall of SC exhibited discontinuities but the basement membrane as seen by QF/DE was much more elaborate and complex than was evident in conventional TEM of immersion-fixed eyes. This basal lamina became less continuous with increasing perfusion pressure.QF/DE, although difficult and very labor-intensive when used to examine the TM, offers several clear advantages over conventional methods of tissue preparation for ultrastructural study. Although a more complex and less open extracellular matrix structure was seen in the JCT using QF/DE compared with conventional TEM, some open-spaces, similar in size to those seen by TEM, were still observed in this region. The continued presence of such open-spaces in QF/DE images suggests that either the JCT may not generate a significant fraction of outflow resistance in normal eyes or even QF/DE is not sensitive enough to preserve and identify all the extracellular matrix in the JCT region of the TM.SC appears to exhibit a discontinuous basal lamina like lymphatic channels but, like venules, exhibits a wide lumen and continuous endothelium. Because of these features, and the presence of continuous tight junctions that typify continuous capillaries, but neither lymphatic channels nor venules, SC has traditionally been described as a vessel sui generis. Our observations of perfusion-induced changes in the basal lamina of the inner wall of SC suggest that the discontinuous basal lamina underlying the inner wall of SC may not represent the normal expression of the vessel but may simply be a consequence of the way in which giant vacuoles and their pores give rise to outflow.

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PubMed2002

The mechanism of increasing outflow facility during washout in the bovine eye.

PURPOSE: To investigate the relationship between outflow facility and separation between the inner wall of the aqueous plexus and the juxtacanalicular connective tissue (JCT) during washout in the bovine eye. METHODS: Facility was recorded during 3 hours of anterior chamber perfusion at 15 mm Hg in eight pairs of bovine eyes. One eye of each pair was then lowered to 0 mm Hg for 1 hour, whereas the fellow eye was kept at 15 mm Hg. After a brief perfusion at 15 mm Hg, both eyes were perfusion fixed and processed for electron microscopy. Micrographs of the inner wall were analyzed for separation from the JCT. To study the role of cellular adhesion between the inner wall and JCT, 12 additional pairs were perfused with integrin-binding peptide (RGD: Arg-Gly-Asp) or sham control peptide (RGE: Arg-Gly-Glu) at 2 micro M to 2 mM, before IOP was reduced. RESULTS: During the first 3 hours, facility increased in both eyes because of "washout." However, after 1 hour of 0 mm Hg, facility decreased by 13% (P < 0.006), whereas facility increased by 20% (P < 0.001) in the fellow eyes maintained at 15 mm Hg. Two types of separation were observed between the inner wall and JCT: cell-matrix separation between the endothelial cell and basal lamina and matrix-matrix separation between the basal lamina and JCT. A significant positive correlation (P = 0.042) was found between the degree of matrix-matrix separation and the change in outflow facility after 1 hour of 0 mm Hg. Compared with RGE control, RGD had no apparent effect on outflow facility (P > 0.35) or on the change in outflow facility after 1 hour at 0 mm Hg (P > 0.15). CONCLUSIONS: The increase in outflow facility that occurs during washout in the bovine eye is reversible and correlates with the degree of separation between the basal lamina of the inner wall endothelium and the JCT. Therefore, adhesions tethering the inner wall to the JCT may be important ultrastructural features involved in the regulation of aqueous humor outflow resistance.

Animals↗
PubMed2000

A Reevaluation of Density-Dependent Population Cycles in Open Systems.

Studies motivated by consideration of barnacle populations have led to the prediction of two different dynamic states for space-limited open populations subject to density-dependent mortality. Population densities may cycle or fluctuate stochastically around a mean value. Despite the potential generality of the associated theory, there are few examples of population cycling in open systems that have been shown to be driven by density-dependent effects. This may be because settlement and growth processes are generally too slow or too variable to generate consistent cycles. An alternative explanation is examined in this article using spatially explicit simulations. Even under conditions of consistent settlement and growth, the cycles predicted in at least one previous study are shown to represent a special case. Clear population cycles are only observed when the density-dependent disturbances are constrained to reoccur in exactly the same location. In the more general case, where density-dependent disturbances respond to local variations in population density, the cycling predicted from simple models is difficult to detect. Hence, a failure to detect cycling in population density does not refute a role for density dependence. Density-dependent disturbances can create a characteristic spatial structure consisting of a mosaic of cohorts.

barnacles↗
PubMedDate not supplied

Using molecular equivalence numbers to visually explore structural features that distinguish chemical libraries.

A molecular equivalence number (meqnum) classifies a molecule with respect to a class of structural features or topological shapes such as its cyclic system or its set of functional groups. Meqnums can be used to organize molecular structures into nonoverlapping, yet highly relatable classes. We illustrate the construction of some different types of meqnums and present via examples some methods of comparing diverse chemical libraries based on meqnums. In the examples we compare a library which is a random sample from the MDL Drug Data Report (MDDR) with a library which is a random sample from the Available Chemical Directory (ACD). In our analyses, we discover some interesting features of the topological shape of a molecule and its set of functional groups that are strongly linked with compounds occurring in the MDDR but not in the ACD. We also illustrate the utility of molecular equivalence indices in delineating the structural domain over which an SAR conclusion is valid.

Journal Article↗