Abstract
Abstract: :
Purpose: As the purinoceptor P2Y2 agonist, INS365, stimulates both fluid transport across rabbit conjunctival tissue and mucin secretion from goblet cells, it is a candidate for dry eye therapy. Therefore, we sought to determine in a short-term rabbit dry eye model whether INS365 containing eye drops could suppress any of the epithelial damage produced by blockage of the blink reflex. Methods: Five min after anesthetization with urethane, either 50 µL of saline or INS365 containing eyedrops were applied to eyes. Rabbits were allowed to blink once 5 min post-application. In the dose response study employing 0.001--1.0% INS365, the eyes were kept open for 3 h. With the time course study, they were kept open from 1 to 3 h. Eyes were extirpated at appropriate times and corneal epithelial integrity was evaluated based on the extent of methylene blue staining in histological sections. Results: After 3 h of desiccation, the amount of extractable dye following sacrifice increased by more than 4-fold in the vehicle-treated eyes. However, in those rabbits treated with 1.0% INS365, dye recovery was invariant. From 0.001% to 1.0% INS365, the relative decreases in staining were concentration dependent. Such decreases were in all cases significant at concentrations greater than 0.1%. Conclusion: These results suggest that INS365 containing eye drops may be of therapeutic value in decreasing the loss of corneal epithelial integrity in dry eye.
Keywords: 376 cornea: tears/tear film/dry eye • 316 animal model • 390 drug toxicity/drug effects