Topographic distribution and phenotypic heterogeneity of Schlemm's canal endothelium in human donor eyes

Endothelium phenotype is known to be closely associated with flow shear stress. This study is to determine the topographic distribution of endothelial cells and the phenotype of different quadrants and regions of Schlemm's canal using human donor eyes. This study infers differences in flow dynamics based on cell shape and intra-cellular structure. The Schlemm's canal from 15 human donor eyes were either perfusion labelled using silver stain or dissected for float labeling with Phalloidin to enable visualization of endothelial cell border and intra-cellular structure. Data were acquired for endothelial cells from the outer and inner wall of Schlemm's canal and grouped according to quadrant of origin. Measurements included endothelial cell length, width, area, and aspect ratio and compared between quadrants. Endothelial cells are mostly spindle-shape and the cell size on the outer wall are larger and longer than those from the inner wall. Significant differences in endothelial cell size and shape were seen in different quadrants. The endothelial cells have varied shapes and orientations close to large ostia in the outer wall and remarkably long endothelial cells were found in the walls of collector channels. F-actin aggregation was found at all endothelial cell borders, and inside some of the endothelial cytoplasm. The presence of various spindle shapes, significant phenotype heterogeneity and F-actin aggregation of endothelial cells in-dicates aqueous humor flow likely creates variations in shear stress within Schlemm's canal. Further investi-gation of the relationship between the phenotype heterogeneity and hydrodynamics of aqueous flow may help us understand the mechanisms of outflow resistance changes in glaucoma.

Automated summary

This study aims to determine the topographic distribution and phenotypes of endothelial cells in different quadrants and regions of Schlemm's canal using human eyes. The results indicate significant differences in cell size and shape between quadrants, with larger and longer cells on the outer wall. The presence of various spindle shapes and F-actin aggregation suggests that aqueous humor flow likely creates variations in shear stress within the canal, which may contribute to changes in outflow resistance in glaucoma.