An adenosine agonist and prostaglandin E1 cause breakdown of the blood- retinal barrier by opening tight junctions between vascular endothelial cells

S. A. Vinores, H. Sen, Peter A Campochiaro

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1870-1878
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume33
Issue number6
StatePublished - 1992

Fingerprint

Blood-Retinal Barrier
Adenosine-5'-(N-ethylcarboxamide)
Tight Junctions
Alprostadil
Adenosine
Endothelial Cells
Retinal Vessels
Injections
Fluorophotometry
Rabbits
Intercellular Junctions
Macular Edema
Cerebral Palsy
Serum Albumin
Epinephrine
Albumins
Electrons
Staining and Labeling
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology

Cite this

@article{bf364a8db80547f4b7d783caf7e59f0a,
title = "An adenosine agonist and prostaglandin E1 cause breakdown of the blood- retinal barrier by opening tight junctions between vascular endothelial cells",
abstract = "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.",
author = "Vinores, {S. A.} and H. Sen and Campochiaro, {Peter A}",
year = "1992",
language = "English (US)",
volume = "33",
pages = "1870--1878",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "6",

}

TY - JOUR

T1 - An adenosine agonist and prostaglandin E1 cause breakdown of the blood- retinal barrier by opening tight junctions between vascular endothelial cells

AU - Vinores, S. A.

AU - Sen, H.

AU - Campochiaro, Peter A

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0026650517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026650517&partnerID=8YFLogxK

M3 - Article

C2 - 1582791

AN - SCOPUS:0026650517

VL - 33

SP - 1870

EP - 1878

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 6

ER -