An adenosine agonist and prostaglandin E1 cause breakdown of the blood-retinal barrier by opening tight junctions between vascular endothelial cells.
Macular edema occurs in several disease processes, but little is known about the mechanisms by which it occurs in any disease process. Previously, the authors showed that intravitreous injection of adenosine agonists, prostaglandin E1 (PGE1), or epinephrine in rabbits, causes breakdown of the blood-retinal barrier (BRB) measured by vitreous fluorophotometry. N-ethylcarboxamidoadenosine (NECA), a nonspecific adenosine agonist, and PGE1, cause much greater breakdown of the BRB than the other agents tested. In this study, rabbit eyes were examined ultrastructurally and electron immunocytochemically for extravascular albumin as an indicator of BRB failure after intravitreous injection of these agents or vehicle alone to investigate potential mechanisms involved in BRB compromise. Six hours after injection, there were significantly more open tight junctions between retinal vascular endothelial cells in NECA-, PGE1-, and adenosine-injected eyes than in vehicle-injected eyes. Immunocytochemical staining for serum albumin showed that many of the junctions that appeared open were functionally open. Forty-eight hours after injection of PGE1 (10(-4) mol/l), the percentage of open vascular endothelial cell tight junctions had returned to that of the control specimens, but the opening of tight junctions by NECA (10(-3) mol/l) did not appear to be reversed after 48 hr. Pinocytotic vesicular transport was prominent in all eyes, and no difference was found between vehicle- and drug-injected eyes. These data suggest that NECA and PGE1 cause breakdown of the BRB, at least in part, by opening tight junctions between retinal vascular endothelial cells.
Vinores
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SA
Wilmer Institute, Johns Hopkins Hospital, Baltimore, Maryland 21205.
Sen
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Campochiaro
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PA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000418:Albumins / Q000648:ultrastructure; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D015590:Fluorophotometry; D007267:Injections; D007365:Intercellular Junctions / Q000187:drug effects* / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D011817:Rabbits; D012171:Retinal Vessels / Q000187:drug effects / Q000648:ultrastructure; D014665:Vasodilator Agents / Q000494:pharmacology*
D000418:Albumins; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D000527:Alprostadil; D000241:Adenosine