title: Expression of the lymphatic marker podoplanin (D2-40) in human fetal eyes.
abstract: During human ocular development, expression of proteins varies in different maturation stages. This study aims to characterize structures in human fetal eyes stained by the lymphatic marker podoplanin (D2-40) with emphasis on the stage of maturation and the presence of intraocular lymphatic structures. Formalin-fixed paraffin-embedded eyes from 40 human fetuses between 10 and 38 weeks of gestation (WoG) were investigated. Immunohistochemical stains were performed for D2-40, LYVE-1 as a secondary lymphatic marker, and CD34 as a control for endothelial reactivity. A semiquantitative analysis of antigen expression in different segments of the eye was performed by light microscopy. The intensity of antigen expression was graded with a score ranging from 0 to 3. Podoplanin expression was found with a variable intensity in 97.5% of the eyes, in particular in lymphatic vessels of the conjunctiva (n = 26), conjunctival and corneal epithelium (n = 33), corneal endothelium (n = 4), trabecular meshwork (n = 28), and optic nerve sheaths (n = 23). A slight, equivocal staining reaction was noted in the choroid (n = 14). There was a correlation of antigen reactivity and the gestational age for corneal endothelial reactivity in earlier gestational stages (p = 0.003) and trabecular meshwork in older eyes (p = 0.031). D2-40 positive Müller cells were detected in two eyes ≥32 WoG. Thus, aside from conjunctival lymphatic vessels, podoplanin was expressed in several structures of the human fetal eye and the ocular adnexae at different gestational stages. Podoplanin positive structures were also found in the choroid and the chamber angle. However, lymphatic vessels or its progenitors could not be unequivocally identified in intraocular structures during 10-38 weeks of gestation. There is no evidence from our data that transient intraocular lymphactics develop in the fetal eye between 10 and 38 weeks of gestation.
authors.affiliation: Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, 53127 Bonn, Germany. Electronic address: martina.herwig@ukb.uni-bonn.de.
authors.forename: Martina C
authors.initials: MC
authors.lastname: Herwig
authors.affiliation: Center of Pediatric Pathology and Pathology, MVZ Venusberg, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. Electronic address: k.muenstermann@gmx.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Münstermann
authors.affiliation: Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany. Electronic address: ute.klarmann-schulz@ukb.uni-bonn.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Klarmann-Schulz
authors.affiliation: Department of Ophthalmology, University of Cologne, Kerpenerstr. 62, 50924 Cologne, Germany. Electronic address: simona.schlereth@uk-koeln.de.
authors.forename: Simona L
authors.initials: SL
authors.lastname: Schlereth
authors.affiliation: Department of Ophthalmology, University of Cologne, Kerpenerstr. 62, 50924 Cologne, Germany. Electronic address: ludwig.heindl@uk-koeln.de.
authors.forename: Ludwig M
authors.initials: LM
authors.lastname: Heindl
authors.affiliation: Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, 53127 Bonn, Germany. Electronic address: karinloeffler@uni-bonn.de.
authors.forename: Karin U
authors.initials: KU
authors.lastname: Loeffler
authors.affiliation: 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.forename: Annette M
authors.initials: AM
authors.lastname: Müller
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003228:Conjunctiva / Q000196:embryology* / Q000378:metabolism; D003315:Cornea / Q000196:embryology* / Q000378:metabolism; D005260:Female; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D007124:Immunoenzyme Techniques; D042601:Lymphatic Vessels / Q000196:embryology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009900:Optic Nerve / Q000196:embryology* / Q000378:metabolism; D016612:Paraffin Embedding; D016707:Tissue Fixation; D014129:Trabecular Meshwork / Q000196:embryology* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D008562:Membrane Glycoproteins; D033921:Vesicular Transport Proteins; C119248:LYVE1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: D2-40; eye; fetus; immunohistochemistry; lymphangiogenesis; ophthalmic pathology; pediatric pathology; podoplanin