November 1995
Volume 36, Issue 12
Free
Articles  |   November 1995
RMP-7, a bradykinin agonist, increases permeability of blood-ocular barriers in the guinea pig.
Author Affiliations
  • P J Elliott
    Alkermes Inc., Los Angeles, California, USA.
  • J B Mackic
    Alkermes Inc., Los Angeles, California, USA.
  • W F Graney
    Alkermes Inc., Los Angeles, California, USA.
  • R T Bartus
    Alkermes Inc., Los Angeles, California, USA.
  • B V Zlokovic
    Alkermes Inc., Los Angeles, California, USA.
Investigative Ophthalmology & Visual Science November 1995, Vol.36, 2542-2547. doi:
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      P J Elliott, J B Mackic, W F Graney, R T Bartus, B V Zlokovic; RMP-7, a bradykinin agonist, increases permeability of blood-ocular barriers in the guinea pig.. Invest. Ophthalmol. Vis. Sci. 1995;36(12):2542-2547.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

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 microgram/kg over 5 minutes) or saline were administered intraarterially into the ocular circulation before either radiolabeled sucrose or ganciclovir (0.4 to 0.6 microCi/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.

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