A new hypothesis on mechanisms of retinal vascular permeability in diabetes

Thomas W. Gardner, Erich Lieth, David A. Antonetti, Alistair Barber

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)peer-review

Abstract

Increased microvascular permeability, a characteristic abnormality in diabetes, is thought to result in microalbuminuria. In this report, Gardner and associates provide evidence that retinal hemorrhages, lipid exudate deposition, and macular edema result from aberrant production of vasoactive agents. Candidate vasoactive factors include histamine and vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Either or both of these substances may be released in excessive amounts after diabetes induced damage to glial cells that support the metabolism of neurons and blood vessels. VEGF/VPF is indicated as having substantive involvement in development of proliferative diabetic retinopathy. Both histamine and VEGF/VPF increase permeability to sodium fluorescein after injection into the vitreous cavity of normal rats. The authors theorize that vasoactive agents may regulate permeability by modifying cellular tight junction proteins of which ZO-1 has been shown to be regulated by histamine. Further, VEGF reduces the amount of occludin, another seven junctional proteins that spans plasma membranes serving as a transmembrane protein permitting cell-to-cell interaction through tight junctions. Diabetic retinopathy may be viewed as a consequence of disturbed cellular metabolism producing vasoactive factors by neurons and/or glia that impact on tight junction proteins. Treatments testing this hypothesis have been designed: a randomized trial of the histamine H1, antagonist, astemizole, to determine whether blocking the effect of histamine will reduce macular edema has begun. As specific antagonists are synthesized, other studios to determine the benefit of interrupting the action of vasodilators on tight junction proteins can be anticipated.
Original languageEnglish (US)
Title of host publicationDiabetic Renal-Retinal Syndrome
EditorsEli A. Friedman, Francis A. L'Esperance Jr.
PublisherSpringer
Pages169-179
ISBN (Electronic)978-94-011-4962-4
ISBN (Print)978-94-010-6083-7
StatePublished - 1998

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