Carboxymethylcellulose binds to human corneal epithelial cells and is a modulator of corneal epithelial wound healing.
OBJECTIVE
In this study, the ability of carboxymethylcellulose (CMC), used in artificial tear formulations, to interact with corneal-epithelial-cells (HCECs) and facilitate corneal epithelial wound healing was investigated.


METHODS
HCECs were incubated with fluorescein-labeled CMC (F-CMC). CMC-epithelial binding was measured by spectrophotometry. The effect on F-CMC binding by hyaluronic acid (HA) or glucose was measured after preincubation in HA, mAb to CD44, or glucose, or mAb to GluT-1. F-CMC binding to fibronectin or collagen was measured by incubating proteins with F-CMC. The wound widths were measured 18 hours after confluent HCECs were scratch wounded. The ability of CMC to induce cell chemotaxis, proliferation, or migration was measured by quantitative assay. The efficacy of CMC in promoting epithelial wound healing was also tested in a rabbit epithelial scrape-wound model.


RESULTS
CMC remained bound to the HCECs for 2 hours. Preincubation of HCECs with glucose or mAb to GluT-1, but not with HA or mAb to CD44, reduced the binding of CMC to HCECs from 43.7% to 67.2% or 10.9% to 25.3%, respectively. CMC bound significantly to fibronectin (3.1-fold) or collagen (9.3-fold) compared with the control (BSA), and such binding enhanced cell adhesion. CMC stimulated re-epithelialization of HCECs scratched in vitro and in vivo rabbit cornea epithelial scrape wounds. CMC stimulated cell migration but not proliferation.


CONCLUSIONS
CMC probably binds to HCECs through interaction of its glucopyranose subunits with glucose transporters. CMC binding to the matrix proteins stimulated HCEC attachment, migration, and re-epithelialization of corneal wounds.
Garrett
Qian
Q
Institute for Eye Research, University of New South Wales, Sydney, NSW 2052, Australia. q.garrett@ier.org.au
Simmons
Peter A
PA
Xu
Shunjiang
S
Vehige
Joseph
J
Zhao
Zhenjun
Z
Ehrmann
Klaus
K
Willcox
Mark
M
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D002266:Carboxymethylcellulose Sodium / Q000378:metabolism* / Q000494:pharmacology; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D019573:Epithelium, Corneal / Q000293:injuries / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D011817:Rabbits; D014945:Wound Healing / Q000187:drug effects*
D005353:Fibronectins; D005456:Fluorescent Dyes; D003094:Collagen; D006821:Hyaluronoglucosaminidase; D005947:Glucose; D002266:Carboxymethylcellulose Sodium