Does the Blood-brain Barrier Play a Role in Glaucoma?

The optic nerve head, although part of the central nervous system, lacks classical blood–brain barrier properties. The tissue of Elschnig does not totally separate the optic nerve head from fenestrated peripapillary choriocapillaries. The microvessels in the prelaminar region of the optic nerve head have less effective barriers than those in the laminar or retrolaminar regions. In glaucoma, the blood–brain barrier in the optic nerve head may even be weaker. Incomplete blood–brain barrier renders circulating molecules, such as endothelin-1 (ET-1), direct access to smooth vascular muscle cells and pericytes both in the prelaminar part of the optic nerve head and to adjacent retinal tissue. This potentially leads to some vasoconstriction as observed in the peri-papillary retinal vessel in glaucoma patients. In extreme situations, this may provoke retinal vein occlusion. The direct access of these molecules also influences the barrier function. If, simultaneously, ET-1 reduces endothelial tight-junctions and matrix-metalloproteinase (MMP)-9 degrades the basement membrane, not only macromolecules but even red blood cells may cross the blood–brain barrier and lead to what is clinically observed as optic disk hemorrhages.