title: Enrichment of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)-positive macrophages around blood vessels in the normal human sclera.
abstract: OBJECTIVE
  To investigate whether the normal adult human sclera contains lymphatic vessels and to study their relation to immune cells and blood vessel anatomy.
  
  
  METHODS
  Scleral tissue probes from 35 adult human donor bulbi were analyzed by immunohistochemistry and confocal microscopy for blood vessels (CD31+), lymphatic vessels (lymphatic vessel endothelial hyaluronan receptor 1 [LYVE1]+, podoplanin+), and macrophages (CD68+) at 12 locations (anterior, equatorial, and posterior at 3, 6, 9, and 12 o'clock positions of the eye) in all three scleral layers (episclera, stroma, and lamina fusca). Approval for scientific examination was obtained.
  
  
  RESULTS
  CD31+ blood vessels were detectable in the human sclera, where the percentage area covered by CD31+ blood vessels was highest in the anterior episclera, followed by equatorial and posterior episclera, and was lowest in the scleral stroma (regardless of location). LYVE1+ podoplanin+ lymphatic vessels were not detectable in any location investigated, although there was a high number of LYVE1+ CD68+ macrophages. These macrophages were concentrated around blood vessels. In contrast, in the episclera, the number of detected LYVE1+ CD68+ macrophages was comparable in all locations; within the stroma, their number increased toward the posterior part of the eye.
  
  
  CONCLUSIONS
  The adult sclera contains blood vessels but lacks, as revealed by immunohistochemistry and confocal microscopy, true lymphatic vessels. LYVE1+ CD68+ macrophages are located adjacent to the longitudinal axis of blood vessels. The function of these cells needs further investigation, but could be a next step toward a better understanding of pathological disorders such as inflammation, tumor, trauma, or glaucoma.
authors.affiliation: Department of Ophthalmology, University of Cologne, Cologne, Germany.
authors.forename: Simona L
authors.initials: SL
authors.lastname: Schlereth
authors.forename: Barbara
authors.initials: B
authors.lastname: Neuser
authors.forename: Albert
authors.initials: A
authors.lastname: Caramoy
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Grajewski
authors.forename: Konrad R
authors.initials: KR
authors.lastname: Koch
authors.forename: Falk
authors.initials: F
authors.lastname: Schrödl
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
authors.forename: Ludwig M
authors.initials: LM
authors.lastname: Heindl
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042601:Lymphatic Vessels / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012590:Sclera / Q000098:blood supply*; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D000097382:CD68 Molecule; D000098853:Podoplanin
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D033921:Vesicular Transport Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C119248:LYVE1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: blood vessels; immunohistochemistry; lymphatic vessels; macrophages; sclera