RMP-7, A BRADYKININ AGONIST, INCREASES PERMEABILITY OF BLOOD-OCULAR BARRIERS IN THE GUINEA-PIG

Purpose. To determine if the bradykinin agonist, RMP-7, could increase the ocular tissue concentration of agents that normally have limited access across the blood-ocular barriers. The extracellular space marker, sucrose, and the anti-viral drug, ganciclovir, were tested. Methods. Using the perfused eye method in guinea pigs, RMP-7 (1 mu g/kg over 5 minutes) or saline were administered intraarterially into the ocular circulation before either radiolabeled sucrose or ganciclovir (0.4 to 0.6 mu Ci/ml per minute). At time intervals ranging from 0.25 minute to 10 minutes, perfused eyes were removed, and the radioactivity within various compartments was measured using liquid scintillography. Results. Pretreatment with RMP-7 significantly increased uptake of both sucrose (up to 4.5-fold) and ganciclovir (up to 2-fold) into the guinea pig retina and lens. Smaller and less consistent effects were observed in other eye compartments. Conclusions. This report demonstrates that RMP-7 enhances the permeability of blood-ocular barriers, and it provides the first pharmacologic evidence for a means to enhance the concentration of ganciclovir into the retina. Thus, these data support the concept that RMP-7 may prove to be a useful adjunct for enhanced delivery of therapeutics to the eye under conditions in which ocular barriers limit treatment.