3D map of the human corneal endothelial cell

Abstract

Corneal endothelial cells (CECs) are terminally differentiated cells, specialized in regulating corneal hydration and transparency. They are highly polarized flat cells that separate the cornea from the aqueous humor. Their apical surface, in contact with aqueous humor is hexagonal, whereas their basal surface is irregular. We characterized the structure of human CECs in 3D using confocal microscopy of immunostained whole corneas in which cells and their interrelationships remain intact. Hexagonality of the apical surface was maintained by the interaction between tight junctions and a submembraneous network of actomyosin, braced like a drum. Lateral membranes, which support enzymatic pumps, presented complex expansions resembling interdigitated foot processes at the basal surface. Using computer-aided design and drafting software, we obtained a first simplified 3D model of CECs. By comparing their expression with those in epithelial, stromal and trabecular corneal cells, we selected 9 structural or functional proteins for which 3D patterns were specific to CECs. This first 3D map aids our understanding of the morphologic and functional specificity of CECs and could be used as a reference for characterizing future cell therapy products destined to treat endothelial dysfunctions.

Transcriptomic analysis of differential gene expression during chick periocular neural crest differentiation into corneal cells

“…The characteristic hexagonal shape of the corneal endothelium is due to forces that straighten the actomyosin fibers on the apical surface that faces the anterior chamber. The apical surface is also marked by ZO‐1, whereas the basal surface that is in contact with the Descemet's membrane is labeled by integrin α3β1 . Of interest, although ZO‐1 ( TJP1 ) is a major component of the adult corneal endothelium, it was not upregulated in our data sets (Supplementary Table S8).…”

“…The apical surface is also marked by ZO-1, whereas the basal surface that is in contact with the Descemet's membrane is labeled by integrin α3β1. 116 Of interest, although ZO-1 (TJP1) is a major component of the adult corneal endothelium, 117,118 it was not upregulated in our data sets ( Supplementary Table S8). Suggesting that its expression and function may arise at a later time point than the stages of corneal development used for this study.…”

Therapeutic efficacy of 3% NaCl hypertonic solution in postoperative corneal edema

“…Строма роговицы должна находиться в состоянии отно-сительной дегидратации, чтобы сохранять одно из основных своих свойств -прозрачность [12]. В случае нарушения водного баланса строма ро-говицы за счёт гликозаминогликанов быстро на-бухает, нарушается правильная организация кол-лагеновых волокон, что в свою очередь приводит к уменьшению прозрачности и снижению остроты зрения [4][5][6].…”

A non-canonical role for p27Kip1 in restricting proliferation of corneal endothelial cells during development

“…The corneal endothelium is a fluid transporting epithelium that is essential for corneal hydration and transparency. Consisting of a monolayer of flat, irregularly-shaped cells with dendrite-like processes, this tissue provides an important physiological interface between the cornea and the adjoining aqueous humor (1)(2)(3)(4)(5)(6)(7). A critical determinant of endothelium function is cell density, which in healthy adult humans generally exceeds 2500 cells/mm 2 (8-9).…”

“…Finally, our evidence showing that the two mutants have opposite effects on cell dispersion within endothelial monolayers confirm previous work documenting the inhibitor's involvement in cell migration and highlight the fact that p27 is able to regulate proliferation and migration in a coordinate fashion during development. 6…”