Hydrostatic Pressure Gradients and a New Membrane-glymphatic Theory of Primary Glaucoma

Abstract

The paper describes a novel theory of primary glaucoma etiopathogenesis based on a new understanding of the glymphatic system of the eye. Glymphatic flow routes of the eye include the vitreous body, uveal tract, paravascular spaces, and the retina. There are different pressure gradients of the intraocular fluid flow within the divided central channel of the vitreous body. In normal conditions above the foveola there is highly positive pressure gradient whereas above the optic disc it is 3 times lower. The retinal pigment epithelium is responsible for water and metabolic exchanges between choroid and the vitreous, therefore may contribute to intra-ocular fluid accumulation. Impairment of the outer blood-ocular and/or blood-aqueous barriers is the key pathogenic element of glaucoma including secondary forms due to uveitis. A disbalance of the pressure gradients above the macula and above the optic disc leads to fluid accumulation above the latter. An abundant intra-retinal fluid flow through the glymphatic pathways in the outer and inner plexiform layers, formed by Muller cell processes, contributes to accumulation of the interstitial fluid before the lamina cribrosa. Excessive interstitial fluid from the retina passes not only through the retinal pigment epithelium to choroid but also through paravascular spaces to the optic disc cup and discharges partly back to the vitreous body through the prevascular vitreous fissures. There is an interstitial fluid flow existing through paravascular spaces, the plexiform layers of retina and along the axons of ganglion cells to the optic nerve and its sheath where excessive fluid is absorbed into the subarachnoid space. The RPE plays a major role in glaucoma etiopahogenesis, probably acting as a regulator of fluid transport in the eye.