Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye.

Abstract

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.

CLINICAL RELEVANCE:

Topically applied C-NAC might protect the ocular surface in dry eye syndrome, as evidenced by decreased inflammatory cytokine expression.

• Authors: Teeravee Hongyok, Jemin J Chae, Young Joo Shin, Daero Na, Li Li, Roy S Chuck
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 127 Issue 4 Pg. 525-32 (Apr 2009) ISSN: 1538-3601 [Electronic] United States
• PMID: 19365035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Ophthalmic Solutions
• RNA, Messenger
• chitosan-N-acetylcysteine conjugate
• rimabotulinumtoxinB
• Chitosan
• Botulinum Toxins
• Botulinum Toxins, Type A
• Fluorometholone
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage, pharmacology)
• Administration, Topical
• Animals
• Blinking (physiology)
• Botulinum Toxins
• Botulinum Toxins, Type A
• Chitosan (administration & dosage, analogs & derivatives, pharmacology)
• Conjunctiva (metabolism)
• Cornea (metabolism)
• Cytokines (genetics, metabolism)
• Disease Models, Animal
• Dry Eye Syndromes (chemically induced, drug therapy, metabolism)
• Female
• Fluorescent Antibody Technique, Indirect
• Fluorometholone (administration & dosage, pharmacology)
• Lacrimal Apparatus (metabolism)
• Mice
• Mice, Inbred CBA
• Ophthalmic Solutions (administration & dosage, pharmacology)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tears (metabolism)