Comparative Anatomy, Physiology and In Vitro Models of the Blood-Brain and Blood-Retina Barrier

Burkhard      Schlosshauer; Heiko      Steuer

Abstract

The blood-brain barrier (BBB) represents a functional interface between the blood stream and the neuronal microenvironment. Distinct cellular and molecular features of brain microvessel endothelial cells result in barrier and carrier functions that guarantee exclusion of adverse components such as neurotoxic metabolites on the one hand and selective passage of essential nutrients on the other hand. Circumventricular organs are brain structures that lack BBB characteristics, allowing for hormone-mediated interactions between e.g. the pituitary and distant organs. The retina, as an integral part of the central nervous system, is enclosed by the pigment epithelium, which functions as a barrier interface between the systemic blood vessels of the neighboring choroid and the retina. Various BBB-specific markers, tight junction components, and carrier systems including amino acid and saccharide transporters have been cloned. P-glycoprotein has been of special interest because this efflux pump counteracts entry of numerous therapeutically relevant drugs into the nervous system. Various in vitro systems of the retinal pigment epithelium (RPE) have been established and employed to analyze pharmacological aspects and pathological cell interactions. The most advanced systems are organotypic cultures and acute preparations of the RPE, i.e. fully intact tissue sheets that can be used as in vivo-like BBB models for transport studies and drug profiling.

Keywords: Blood-Brain, Blood-Retina Barrier, Circumventricular Organs, Astrocytes, Pericytes, P-glycoprotein, Azidothymidine, Multidrug-resistance, Triamcinolone acetonide