2022 Volume 39 Issue 1 Pages 10-17
The pathogenesis of glaucomatous optic neuropathy, especially normal-tension glaucoma, remains controversial. A potent and attractive hypothesis is that the pressure gradient around the lamina cribrosa（translaminar pressure difference）can cause glaucomatous neuropathy. Most clinical studies have reported that normal-tension glaucoma is associated with low cerebrospinal fluid pressure（CSFp）, whereas several other studies have reported the contrary. All these studies were limited to a small number of participants, and the study protocols were not standardized. Therefore, a large-scale clinical study with a non-invasive method of measuring cerebrospinal fluid pressure is required.
Several animal experiments for examining glaucomatous neuropathy caused by lowering cerebrospinal fluid pressure have been conducted. The results from these suggested three mechanisms described below: 1）a pressure gradient between CSFp and intraocular pressure at the cribriform plate could deform the structure of the cribriform plate, leading to the stagnation of axonal flow, 2）low CSFp could directly stagnate axonal flow with chemical or mechanical signal transduction, and 3）disruption in the clearance of toxic substances with a failure of the glymphatic system（lymph duct-like structure consisting of glial cells to excrete CSF outside the brain）due to the pressure gradient within the optic nerve pathway could induce cell death or axonopathy of retinal ganglion. These animal studies are limited in that the structure of the cribriform plate in rodents is immature compared to that in humans, and almost all of these studies involved an acutely lowering cerebrospinal fluid pressure model. However, we could observe the limited but obvious results of retinal ganglion cells’ axonopathy induced by decreasing cerebrospinal fluid volume, thus lowering its pressure. We could utilize these animal models for elucidating the molecular mechanism of glaucomatous neuropathy caused by low cerebrospinal fluid pressure, although well-elaborated animal models including chronic low cerebrospinal fluid pressure models also need to be developed.
