Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye.
OBJECTIVE
To evaluate the effect of a thiolated polymer lubricant, chitosan-N-acetylcysteine conjugate (C-NAC), in a mouse model of dry eye.


METHODS
Eye drops containing 0.5% C-NAC, 0.3% C-NAC, a vehicle (control group), artificial tears, or fluorometholone were applied in a masked fashion in a mouse model of induced dry eye from 3 days to 4 weeks after botulinum toxin B injection. Corneal fluorescein staining was periodically recorded. Real-time reverse transcriptase-polymerase chain reaction and immunofluorescence staining were performed at the end of the study to evaluate inflammatory cytokine expressions.


RESULTS
Mice treated with C-NAC, 0.5%, and fluorometholone showed a downward trend that was not statistically significant in corneal staining compared with the other groups. Chitosan-NAC formulations, fluorometholone, and artificial tears significantly decreased IL-1beta (interleukin 1beta), IL-10, IL-12alpha, and tumor necrosis factor alpha expression in ocular surface tissues.


CONCLUSIONS
The botulinum toxin B-induced dry eye mouse model is potentially useful in evaluating new dry eye treatment. Evaluation of important molecular biomarkers suggests that C-NAC may impart some protective ocular surface properties. However, clinical data did not indicate statistically significant improvement of tear production and corneal staining in any of the groups tested.


CONCLUSIONS
Topically applied C-NAC might protect the ocular surface in dry eye syndrome, as evidenced by decreased inflammatory cytokine expression.
Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Teeravee
T
Hongyok
Jemin J
JJ
Chae
Young Joo
YJ
Shin
Daero
D
Na
Li
L
Li
Roy S
RS
Chuck
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D001767:Blinking / Q000502:physiology; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003228:Conjunctiva / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005469:Fluorometholone / Q000008:administration & dosage / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013666:Tears / Q000378:metabolism
D016207:Cytokines; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; C540141:chitosan-N-acetylcysteine conjugate; C096323:rimabotulinumtoxinB; D048271:Chitosan; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; D005469:Fluorometholone; D000111:Acetylcysteine