The functional morphology of the outflow systems of ocular and cerebrospinal fluids

Abstract

The drainage pathway of aqueous hmnour of the eye and cerebrospinal fluid (CSF) of the brain has been investigated with and without experimental procedures; and the appropriate tissues have been analysed by light-, scanning- and transmission-electron microscopy to unravel the structural basis for the resistance to, and the precise mechanism of, the outflow of these fluids. The close similarities in the origin, circulation, dynamics and drainage of the humours of the eye and brain are emphasized. In both cases, controversy has centred upon whether or not there are pores in the mesothelial lining of the canal of Schlemm and arachnoid villi which mediate the final outflow of aqueous humour and CSF respectively. Morphometrically, as revealed by scanning electron microscopy, the mesothelial lining of Schlemm's canal and the arachnoid villi are closely comparable, both being constituted by spindle-shaped cells measuring some 40–120 µm in length and 4µ12µm in width in the central region corresponding to one or more apical bulges. Transmission electron microscopy showed that in both cases the mesothelial lining forms a continuous single-layered membrane with adjacent cells joined by junctional complexes offering a restraint to the passage of experimentally introduced colloidal molecules of 10 nm or smaller size. The cells contain an apically bulging nucleus and a moderate amount of the usual intracelhdar organelles including a system of well developed cytoplasmic microfilaments presumably associated with a contractile function. The special feature of many lining cells of both Schlemm's canal and arachnoid villi is the presence of giant vacuolar structures of several micrometers in size. Arguments are advanced that these unit membrane-bound configurations are a real morphological entity and not a product of postmortem or fixation artefact. Morphogenetically, they are considered as developing from surface infoldings or invaginations on the basal aspect of the lining cells, which, by gradually enlarging, eventually open on to the apical cell surface thus cleaving the cells to form wide vacuolar transcellular channels of heterogenous dimensions with basal openings up to 4µm and apical openings up to 2·5µm in size. Our correlative physiological and morphological studies using a variety of tracer substances have shown that the bulk outflow of aqueous humour and of CSF takes place down a pressure gradient via the vacuolar transcellular channels which constitute a dynamic system of pores and act as one-way valves allowing fluid to pass from basal to apical aspects far more easily than in the reverse direction. According to this hypothesis the process of vacuolation is cyclical, and it would now seem certain that this delicate and probably pressure-sensitive vacuolation cycle, in providing the requisite number of pores at any given time, is a controlling factor in the bulk outflow of aqueous humour and CSF, and consequently in the maintenance of normal fluid pressure in the eye and brain. The role of various factors, especially hydrostatic pressure gradient, in influencing the vacuolation cycle is discussed. In contrast to the open passage provided by the unique biological system of vacuolar transcellular channels, other processes, e.g. micropinocytosis, passage through intercellular clefts or small diaphragmed fenestrations, phagocytosis, etc., would normally appear to make a relatively minor contribution in the bulk clearance of the humours of the eye and brain. Our comparative morphological and physiological studies of the eyes of a wide variety of sub-primate vertebrates have further resolved the age-old controversy between morphologists and physiologists, the former concluding a fimdamental difference between primates and lower mammals and the latter contending the essential similarity. Despite gross morphological differences in the configuration of the angle of the anterior chamber, it is shown that, apart from minor variations, there exists throughout the vertebrates an angular aqueous plexus or sinus (analogous to the canal of Schlemm in primate eyes) and that the bulk outflow of aqueous humour takes place across the mesothelial barrier of these aqueous plexuses via vacuolar transcellular channels in a manner exactly comparable to primates. Although an extensive analysis of arachnoid villi in sub-primate species has not been completed, preliminary studies indicate that macrovacuolar configurations may similarly be involved in the bulk outflow of CSF in a wide variety of vertebrates.