Problems in CSF and Ophthalmic Disease Research

There has been significant interest and progress in the understanding of cerebrospinal fluid pressure and its relationship to glaucoma and other ophthalmic diseases. However, just as every physiologic fluid pressure fluctuates, cerebrospinal fluid pressure (CSFP) is similarly dynamic. Coupling this with the difficulty in measuring the pressure, there are many obstacles in furthering this field of study. This review highlights some of the difficulties in CSFP research, including fluid compartmentalization, estimation equations, and pressure fluctuation. Keeping these limitations in mind will hopefully improve the quality and context of this burgeoning field

A new glaucoma hypothesis:a role of glymphatic system dysfunction

In a recent review article titled "A new look at cerebrospinal fluid circulation", Brinker et al. comprehensively described novel insights from molecular and cellular biology as well as neuroimaging research, which indicate that cerebrospinal fluid (CSF) physiology is much more complex than previously believed. The glymphatic system is a recently defined brain-wide paravascular pathway for CSF and interstitial fluid exchange that facilitates efficient clearance of interstitial solutes, including amyloid-beta, from the brain. Although further studies are needed to substantiate the functional significance of the glymphatic concept, one implication is that glymphatic pathway dysfunction may contribute to the deficient amyloid-beta clearance in Alzheimer's disease. In this paper, we review several lines of evidence suggesting that the glymphatic system may also have potential clinical relevance for the understanding of glaucoma. As a clinically acceptable MRI-based approach to evaluate glymphatic pathway function in humans has recently been developed, a unique opportunity now exists to investigate whether suppression of the glymphatic system contributes to the development of glaucoma. The observation of a dysfunctional glymphatic system in patients with glaucoma would provide support for the hypothesis recently proposed by our group that CSF circulatory dysfunction may play a contributory role in the pathogenesis of glaucomatous damage. This would suggest a new hypothesis for glaucoma, which, just like Alzheimer's disease, might be considered then as an imbalance between production and clearance of neurotoxins, including amyloid-beta

Large-scale morphometry of the subarachnoid space of the optic nerve.

BACKGROUND The meninges, formed by dura, arachnoid and pia mater, cover the central nervous system and provide important barrier functions. Located between arachnoid and pia mater, the cerebrospinal fluid (CSF)-filled subarachnoid space (SAS) features a variety of trabeculae, septae and pillars. Like the arachnoid and the pia mater, these structures are covered with leptomeningeal or meningothelial cells (MECs) that form a barrier between CSF and the parenchyma of the optic nerve (ON). MECs contribute to the CSF proteome through extensive protein secretion. In vitro, they were shown to phagocytose potentially toxic proteins, such as α-synuclein and amyloid beta, as well as apoptotic cell bodies. They therefore may contribute to CSF homeostasis in the SAS as a functional exchange surface. Determining the total area of the SAS covered by these cells that are in direct contact with CSF is thus important for estimating their potential contribution to CSF homeostasis. METHODS Using synchrotron radiation-based micro-computed tomography (SRµCT), two 0.75 mm-thick sections of a human optic nerve were acquired at a resolution of 0.325 µm/pixel, producing images of multiple terabytes capturing the geometrical details of the CSF space. Special-purpose supercomputing techniques were employed to obtain a pixel-accurate morphometric description of the trabeculae and estimate internal volume and surface area of the ON SAS. RESULTS In the bulbar segment, the ON SAS microstructure is shown to amplify the MECs surface area up to 4.85-fold compared to an "empty" ON SAS, while just occupying 35% of the volume. In the intraorbital segment, the microstructure occupies 35% of the volume and amplifies the ON SAS area 3.24-fold. CONCLUSIONS We provided for the first time an estimation of the interface area between CSF and MECs. This area is of importance for estimating a potential contribution of MECs on CSF homeostasis

Lipocalin-like Prostaglandin D Synthase in Subretinal Fluid of Detached Retinas in Humans

L-PGDS is a dominancly brain derived protein in the cerebrospinal fluid (CSF) with a low concenrration in serum. L-PGDS has also been demonstrated in the ciliarybodyand me retinal pigmentepithelium in rats. This study demonstrates for the first time L-PGDS in the human SRF of rhegmatogenous retinal detachmemt

Is Normal Tension Glaucoma Related to Altered CSF-Dynamics and Composition?

Cerebrospinal fluid (CSF) is thought to be homogeneous in composicion and to be distributed evenly with a continuous flow through all CSF spaces including the subarachoid space (SAS) of the optic nerve (ON). This concept has been challenged based on the measurement of a marked concentration gradient of the brain-derived protein betatrace (L-PGDS) between the spinal CSF and the CSF in the SAS surrounding the ON in patients with idiopathic imracranial hypertension (IIH), optic nerve sheath meningioma and non-artericic anterior ischemic optic neuropathy and normal tension glaucoma