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The etiology of the majority of defects of the outflow pathways of aqueous humor (glaucoma) and cerebrospinal fluid absorption (hydrocephalus) is unknown. A considerable amount of evidence indicates that glycosaminoglycans have a role in regulating fluid movement through connective tissues such as the trabecular meshwork of the eye and the arachnoid of the brain. Both the eye and the brain outflow pathways have hyaluronic acid and chondroitin sulfate within the filtration barrier. The physiological significance of glycosaminoglycans in the outflow pathways may be their ability to form highly viscous and elastic gel-like solutions that function as a selective biological gel filtration system, which maintains normal intraocular and intracranial pressure. We suggest that glycosaminoglycans may act to maintain the unidirectional character, low-flow fluid movement, and pressure gradient between the trabecular lamellae and the drainage channels of the eye and the brain. This review of the outflow pathways of the eye and the brain discusses the cell biology of glycosaminoglycans in regulating normal aqueous outflow and cerebrospinal fluid absorption.
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