Lack of blood-brain barrier properties in microvessels of the prelaminar optic nerve head.
OBJECTIVE
To define the blood-brain barrier (BBB) characteristics of microvessels in the optic nerve head (ONH).


METHODS
Immunohistochemical staining of different regions of the ONH, retro-laminar optic nerve, and retina of human and monkey eyes was carried out, using antibodies against BBB markers (glucose transporter 1, transferrin receptor, and P-glycoprotein), the non-BBB marker PAL-E, and against plasma proteins fibrinogen and IgG, which serve as endogenous markers of nonspecific microvascular permeability. In the ONH of monkey eyes, the number of transport-related endothelial pinocytotic vesicles and their cellular distribution within the microvessels were determined by electron microscopy.


RESULTS
In both human and monkey eyes, only microvessels in the prelaminar region of the ONH were positive for the PAL-E antigen. The prelaminar region microvessels showed either no or weak expression of the transferrin receptor and P-glycoprotein but stained positive for glucose transporter 1. In human ONH, fibrinogen and IgG were present around microvessels in the prelaminar region but not in other parts of the optic nerve or retina. By electron microscopy, endothelial cells of prelaminar region microvessels contained a higher number of pinocytotic vesicles, located at the luminal and abluminal side of the endothelial cell membrane, in contrast to a mainly abluminal localization in microvessels of the retina and other parts of the optic nerve.


CONCLUSIONS
Microvessels in the prelaminar region of the ONH lack classical BBB characteristics and display nonspecific permeability, possibly mediated by vesicular transport.
Department of Ophthalmology, Academic Medical Center, University of Amsterdam, The Netherlands.
P
P
Hofman
P
P
Hoyng
F
F
vanderWerf
G F
GF
Vrensen
R O
RO
Schlingemann
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D001812:Blood-Brain Barrier; D002196:Capillaries / Q000737:chemistry / Q000166:cytology*; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D051272:Glucose Transporter Type 1; D006801:Humans; D007124:Immunoenzyme Techniques; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000032:analysis; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009898:Optic Disk / Q000098:blood supply* / Q000737:chemistry; D011990:Receptors, Transferrin / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015415:Biomarkers; D001798:Blood Proteins; D051272:Glucose Transporter Type 1; C408608:LRIT1 protein, human; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D011990:Receptors, Transferrin; C495677:SLC2A1 protein, human