[Cytotoxicity evaluation of three tear substitutes used in the treatment of dry eye syndromes].
OBJECTIVE
To investigate cell tolerance of three tear substitutes used in the treatment of dry eye syndromes.


METHODS
Cytotoxicity tests were done on a continuous human conjunctival cell line using microplate cold light cytofluorimetry. Membrane integrity, DNA condensation and reactive oxygen species (ROS) production (hydrogen peroxyde and superoxide anion) were evaluated after 15 minutes of treatment or 15 minutes and 24 hours of cell recovery. Hyaluronic acid, hydroxypropyl methylcellulose associated with sodium perborate (HPMC) and carbomer 934P were tested at their commercial concentrations (respectively 0.18%, 0.3% and 0.3%) and after a 1/10 dilution.


RESULTS
Cell viability and chromatin condensation were not altered by hyaluronic acid for all concentrations and times tested. A decrease in membrane integrity was observed with 0.3% carbomer 934P after 24 hours of cell recovery and with 0.3% HPMC after 15 minutes. This decrease was amplified after 24 hours and associated with an apoptotic phenomenon. A H(2)O(2) production was observed with HPMC associated with sodium perborate and an O(2) production was found with hyaluronic acid diluted at 1/10.


CONCLUSIONS
Hyaluronic acid, carbomer and HPMC are in vitro well-tolerated even if HPMC induces a more important decrease of cell viability compared to the other drugs. Hyaluronic acid, with its rheologic properties, with no in vitro toxicity, seems to be efficient for dry eye patients.
Debbasch
C
C
Unité de Pharmaco-Toxicologie Cellulaire, CHNO des Quinze-Vingts, 28, rue de Charenton 75012 Paris.
Pisella
P J
PJ
Rat
P
P
Warnet
J M
JM
Baudouin
C
C
D001881:Borates / Q000633:toxicity; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects; D015352:Dry Eye Syndromes / Q000628:therapy*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D005609:Free Radicals; D006801:Humans; D006820:Hyaluronic Acid / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000032:analysis; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000633:toxicity; D009883:Ophthalmic Solutions / Q000633:toxicity*; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000032:analysis; D013997:Time Factors
D001881:Borates; D002843:Chromatin; D005609:Free Radicals; D009883:Ophthalmic Solutions; D017382:Reactive Oxygen Species; D013481:Superoxides; D065347:Hypromellose Derivatives; D006820:Hyaluronic Acid; D008747:Methylcellulose; D006861:Hydrogen Peroxide; C027707:sodium perborate