title: Absence of lymphatic vessels in the developing human sclera.
abstract: The adult sclera is free of lymphatic vessels, but contains a net of blood vessels. Whether and when this selectively lymphangiogenic privilege is achieved during embryologic development is not known yet. Therefore, we investigated the developing human sclera for blood- and lymphatic vessels in 34 abortions/stillborns (12-38 weeks of gestation). The probes were subdivided into three groups (group 1: 12-18 weeks of gestation, n = 10; group 2: 19-23 weeks of gestation, n = 13; group 3: 24-38 weeks of gestation, n = 11), and prepared for paraffin sections followed by immunohistochemistry against CD31 to detect blood vessels, and against lymphatic vessel endothelial hyaluronan receptor-1 (LYVE1)/podoplanin to detect lymphatic vessels. We could show, that in the human episclera distinct CD31 + blood vessels are present as early as week of gestation 13. Their amount increased during pregnancy, whereas stromal CD31 + blood vessels were elevated in early pregnancy and regressed with ongoing pregnancy. In the lamina fusca CD31 + blood vessels were absent at any time point investigated. Single LYVE1 + cells were identified primarily in the episclera; their amount decreased significantly with increasing gestational ages (group 1 compared to group 3: p < 0.01). However, LYVE1+/podoplanin + lymphatic vessels were not detectable in the sclera at any gestational ages analyzed. In contrast to the conjunctiva where LYVE1+/podoplanin + lymphatic vessels were detectable as early as week 17, the amount of LYVE1 + cells in the sclera was highest in early pregnancy (group 1), with a significant decrease during continuing pregnancy (p < 0.001). These findings are the first evidence for a fetal lymphangiogenic privilege of the sclera and show, that the fetal human sclera contains CD31 + blood vessels, but is primarily alymphatic. Our findings suggest a strong expression of selectively antilymphangiogenic factors, making the developing sclera a potential model to discern antilymphangiogenic mechanisms.
authors: Department of Ophthalmology, University of Cologne, Kerpenerstr. 62, 50924 Cologne, Germany. Electronic address: Simona.Schlereth@uk-koeln.de.
authors: Simona L
authors: SL
authors: Schlereth
authors: Department of Ophthalmology, University of Cologne, Kerpenerstr. 62, 50924 Cologne, Germany. Electronic address: b.neuser-erftstadt@t-online.de.
authors: Barbara
authors: B
authors: Neuser
authors: Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, 53127 Bonn, Germany. Electronic address: Martina.Herwig@ukb-uni-bonn.de.
authors: Martina C
authors: MC
authors: Herwig
authors: Center of Pediatric Pathology and Pathology, MVZ Venusberg, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. Electronic address: Annette.Mueller@ukb.uni-bonn.de.
authors: Annette M
authors: AM
authors: Müller
authors: Department of Ophthalmology, University of Cologne, Kerpenerstr. 62, 50924 Cologne, Germany. Electronic address: Konrad.Koch@uk-koeln.de.
authors: Konrad R
authors: KR
authors: Koch
authors: Department of Ophthalmology and Anatomy, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria. Electronic address: h.reitsamer@salk.at.
authors: Herbert A
authors: HA
authors: Reitsamer
authors: Department of Ophthalmology and Anatomy, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria. Electronic address: f.schroedl@salk.at.
authors: Falk
authors: F
authors: Schrödl
authors: Department of Ophthalmology, University of Cologne, Kerpenerstr. 62, 50924 Cologne, Germany. Electronic address: Claus.Cursiefen@uk-koeln.de.
authors: Claus
authors: C
authors: Cursiefen
authors: Department of Ophthalmology, University of Cologne, Kerpenerstr. 62, 50924 Cologne, Germany. Electronic address: Ludwig.Heindl@uk-koeln.de.
authors: Ludwig M
authors: LM
authors: Heindl
mesh_terms: D005260:Female; D005865:Gestational Age; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000196:embryology* / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012590:Sclera / Q000098:blood supply / Q000196:embryology*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C119248:LYVE1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D033921:Vesicular Transport Proteins
keywords: angiogenesis; development; fetal; lymphangiogenesis; neovascularization; sclera