Abstract
Abstract: :
Purpose: During the course of regulatory toxicology studies of a compound with alpha1 agonist properties, interstitial and superficial keratitis was observed without any noticeable reduction in tear production occuring as the Schirmer test remained normal and the integrity of the endothelium was maintened. The origin of these changes was suspected to be mediated by the tears, due to an alteration in tear composition. It is known that modifications especially in lysozyme and/or lactoferrin content of tears may lead to keratitis by proliferation of infectious organisms in the fornix and in the tear secretion itself. To our knowledge the composition of canine tears has not been elucidated and it was therefore decided to perform a specific study to characterize normal canine tear composition and possible changes induced by administration of the alpha1 agonist compound. Methods: Two groups of six 7 to 12 month old Beagle dogs (3 males – 3 females per group) were constituted. A control group received the vehicle, and the treated group received 12 mg/kg/day for 31 days. The electrophoretic profile of sampled tears was produced to compare any variations present before and after treatment with the compound. Besides, a proteomic analysis of control tears to characterize the lysozyme was performed. Results: Results showed that although the migration profile of the different electrophoretic peaks was different in the dog relative to man, 5 main peaks were identifiable, and were entitled alpha, beta, gamma, delta and epsilon. By molecular weight separation, the epsilon peak was characterized as that which corresponded to the lysozyme. The lactoferrin peak characterization is on progress. After a 14 day dosing period, decreases were seen in certain of these peaks in comparison with initial baseline values : total proteins –41%, beta peak –40%, gamma peak –39% and epsilon peak (lysozyme) –41%. Conclusions: These alterations indicated a quantitative change in the composition of canine tears following the administration of an alpha1 agonist compound and confirmed that a possible mechanism for the induction of keratitis in the dog could be the decrease in the lysozyme content of tears.
Keywords: cornea: tears/tear film/dry eye • keratitis • drug toxicity/drug effects