Blood‐eye barriers in the rat: Correlation of ultrastructure with function

Abstract

The function of different vascular beds in the rat eye and brain was evaluated by measuring the transfer of a vascular tracer, 14C-alpha-amino-isobutyric acid, from blood to tissue. The density of vascular pores was measured in electron micrographs of perfusion-fixed, age-matched tissue to determine whether the differences in tracer transfer were paralleled by differences in ultrastructure. Tracer transfer in retina was approximately four times that in brain of the same animal. The transfer constant was not changed by the inclusion of cold alpha-amino-isobutyric acid, showing that transport across retinal vessels is not saturable, and indicating that, as in brain, transport is due to passive diffusion. Ultrastructurally, retinal vessels have a higher density of interendothelial junctions and of endothelial vesicles, both of which suggest higher vascular permeability. However, pericytes, which contribute to a second line of defence in the blood-brain barrier, are approximately four times as numerous in retina as in brain, and we suggest that in the retina, they act to compensate for a more permeable endothelial barrier. Ciliary body vessels had a high transfer of tracer, probably as a consequence of the fenestrations in their walls. Iridial vessels had a relatively low transfer of tracer, similar to that in retina even though a proportion of the interendothelial junctions in iridial vessels had expanded junctional clefts suggestive of open paracellular channels. However, both iris and ciliary body may lose tracer to the anterior chamber fluid, leading us to underestimate the vascular permeability in these sites.

Labelling of retinal microglial cells following an intravenous injection of a fluorescent dye into rats of different ages

“…It is speculated that RhIc had readily gained access into the retinal tissues by direct and massive diffusion rather than active transendothelial transportation as was reported in the brain (Xu et al 1993). This is supported by the study of Stewart & Tuor (1994), who demonstrated that the blood-retina barrier (BRB) was 4 times more permeable than the blood-brain barrier (BBB) by measuring the transfer of a vascular tracer, "%C-AIB from blood to tissue ; a similar phenomenon was also reported by other authors (Alm & Tornquist, 1981 ;Ennis & Betz, 1986). It is suggested that the extravasated RhIc in the retinal tissues was readily endocytosed by the resident microglia.…”

Endothelial glycoconjugates: a comparative lectin study of the brain, retina and myocardium

“…Vesicular profiles are very common in somatic capillaries (Simionescu & Simionescu, 1984 ;Simionescu et al 1985). By contrast, these structures are relatively sparse in capillaries of brain and retina (Stewart & Tuor, 1994), suggesting that under . Similarly Allo A labelling of brain microvessels is weak (c) but after neuraminidase treatment is strong (d).…”

Soft Glucocorticoids: Eye-Targeted Chemical Delivery Systems (CDSs) and Retrometabolic Drug Design: A Review

“…For the therapeutic treatment of most of ocular problems, topical administration undoubtedly seems preferred mode, because for systemically administered drugs, only a very small fraction of the total dose will reach the eye from the general circulatory system. Even distribution for this fraction to the inside of the eye is further hindered by the blood-retinal barrier (BRB), which is almost as effective as blood-brain barrier (BBB) in restricting the passage of xenobiotics from the blood stream [34]. Therefore despite its apparent accessibility, the eye, in fact, is well protected against the absorption of foreign materials, including drug molecules, by the eyelids, by flow of tears, and also by the permeability barriers imposed by the cornea on one side and the blood-retinal barrier on the other side as mentioned above [24].…”

“…From the various soft -blockers developed along these lines by Bodor and Buchwald [24], Adaprolol (33), an adamantane ethyl ester was selected as a potential candidate for a new topical antiglaucoma agent [24 ]. The metabolism of the well-known  -blocker Metoprolol (34) has been compared with that of the soft  -blocker Adaprolol which has been designed starting from one of Metoprolol`s inactive acid metabolite (35), viz., phenyl acetic acid (Figure 4). Its other metabolites include -hydroxymetoprolol (36) and ODimethylmetoprolol (37) both of which are active.…”

“…Therefore, it was possible to separate local activity from undesired systemic cardiovascular or pulmonary activity, a characteristic highly desirable in development of antiglaucoma therapy [24]. Adaprolol (33) could be now a potent antiglaucoma soft  -blocker to replace the traditional  -blocker Metoprolol (34). Further clinical studies confirmed that Adaprolol is not only effective in reducing intraocular pressure (IOP) but also has a safer cardiovascular profile than Timolol (27) because unlike Timolol, Adaprolol did not reduce the systolic blood pressure [24].…”