Cargando…

Lymphatic vessels identified in failed corneal transplants with neovascularisation

BACKGROUND: Corneal transplant failure with neovascularisation is a leading indication for full-thickness grafts in patients. Lymphangiogenesis is implicated in the pathology of graft failure, and here we systematically evaluate failed human corneal transplants with neovascularisation for the presen...

Descripción completa

Detalles Bibliográficos
Autores principales: Diamond, Michael Adam, Chan, Sze Wah Samuel, Zhou, Xun, Glinka, Yelena, Girard, Eileen, Yucel, Yeni, Gupta, Neeru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579550/
https://www.ncbi.nlm.nih.gov/pubmed/30348644
http://dx.doi.org/10.1136/bjophthalmol-2018-312630
_version_ 1783427877811781632
author Diamond, Michael Adam
Chan, Sze Wah Samuel
Zhou, Xun
Glinka, Yelena
Girard, Eileen
Yucel, Yeni
Gupta, Neeru
author_facet Diamond, Michael Adam
Chan, Sze Wah Samuel
Zhou, Xun
Glinka, Yelena
Girard, Eileen
Yucel, Yeni
Gupta, Neeru
author_sort Diamond, Michael Adam
collection PubMed
description BACKGROUND: Corneal transplant failure with neovascularisation is a leading indication for full-thickness grafts in patients. Lymphangiogenesis is implicated in the pathology of graft failure, and here we systematically evaluate failed human corneal transplants with neovascularisation for the presence of lymphatic vessels. METHODS: Nine failed grafts with neovascularisation, based on H&E staining with subsequent immunoperoxidase staining for CD31, a blood vessel marker, were selected. Lymphatics were investigated by immunohistochemical and immunofluorescence approaches using podoplanin as a lymphatic marker. In two of nine cases, fluorescence in situ hybridisation (FISH) was used for detection of lymphatic mRNAs including podoplanin, VEGFR-3 and LYVE-1. All immunofluorescence and FISH samples were compared with positive and negative controls and visualised by confocal microscopy. RESULTS: Corneal neovascularisation was established in all cases by H&E and further confirmed by CD31 immunoreactive profiles. Immunohistochemistry for the podoplanin antibody was positive in all cases and showed morphologies ranging from distinct luminal structures to elongated profiles. Simultaneous immunofluorescence using CD31 and podoplanin showed lymphatic vessels distinct from blood vessels. Podoplanin immunofluorescence was noted in seven of nine cases and revealed clear lumina of varying sizes, in addition to lumen-like and elongated profiles. The presence of lymphatic mRNA was confirmed by FISH studies using a combination of at least two of podoplanin, VEGFR-3 and LYVE-1 mRNAs. CONCLUSIONS: The consistent finding of lymphatic vessels in failed grafts with neovascularisation implicates them in the pathogenesis of corneal transplant failure, and points to the lymphatics as a potential new therapeutic target.
format Online
Article
Text
id pubmed-6579550
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-65795502019-07-02 Lymphatic vessels identified in failed corneal transplants with neovascularisation Diamond, Michael Adam Chan, Sze Wah Samuel Zhou, Xun Glinka, Yelena Girard, Eileen Yucel, Yeni Gupta, Neeru Br J Ophthalmol Laboratory Science BACKGROUND: Corneal transplant failure with neovascularisation is a leading indication for full-thickness grafts in patients. Lymphangiogenesis is implicated in the pathology of graft failure, and here we systematically evaluate failed human corneal transplants with neovascularisation for the presence of lymphatic vessels. METHODS: Nine failed grafts with neovascularisation, based on H&E staining with subsequent immunoperoxidase staining for CD31, a blood vessel marker, were selected. Lymphatics were investigated by immunohistochemical and immunofluorescence approaches using podoplanin as a lymphatic marker. In two of nine cases, fluorescence in situ hybridisation (FISH) was used for detection of lymphatic mRNAs including podoplanin, VEGFR-3 and LYVE-1. All immunofluorescence and FISH samples were compared with positive and negative controls and visualised by confocal microscopy. RESULTS: Corneal neovascularisation was established in all cases by H&E and further confirmed by CD31 immunoreactive profiles. Immunohistochemistry for the podoplanin antibody was positive in all cases and showed morphologies ranging from distinct luminal structures to elongated profiles. Simultaneous immunofluorescence using CD31 and podoplanin showed lymphatic vessels distinct from blood vessels. Podoplanin immunofluorescence was noted in seven of nine cases and revealed clear lumina of varying sizes, in addition to lumen-like and elongated profiles. The presence of lymphatic mRNA was confirmed by FISH studies using a combination of at least two of podoplanin, VEGFR-3 and LYVE-1 mRNAs. CONCLUSIONS: The consistent finding of lymphatic vessels in failed grafts with neovascularisation implicates them in the pathogenesis of corneal transplant failure, and points to the lymphatics as a potential new therapeutic target. BMJ Publishing Group 2019-03 2018-10-22 /pmc/articles/PMC6579550/ /pubmed/30348644 http://dx.doi.org/10.1136/bjophthalmol-2018-312630 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Laboratory Science
Diamond, Michael Adam
Chan, Sze Wah Samuel
Zhou, Xun
Glinka, Yelena
Girard, Eileen
Yucel, Yeni
Gupta, Neeru
Lymphatic vessels identified in failed corneal transplants with neovascularisation
title Lymphatic vessels identified in failed corneal transplants with neovascularisation
title_full Lymphatic vessels identified in failed corneal transplants with neovascularisation
title_fullStr Lymphatic vessels identified in failed corneal transplants with neovascularisation
title_full_unstemmed Lymphatic vessels identified in failed corneal transplants with neovascularisation
title_short Lymphatic vessels identified in failed corneal transplants with neovascularisation
title_sort lymphatic vessels identified in failed corneal transplants with neovascularisation
topic Laboratory Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579550/
https://www.ncbi.nlm.nih.gov/pubmed/30348644
http://dx.doi.org/10.1136/bjophthalmol-2018-312630
work_keys_str_mv AT diamondmichaeladam lymphaticvesselsidentifiedinfailedcornealtransplantswithneovascularisation
AT chanszewahsamuel lymphaticvesselsidentifiedinfailedcornealtransplantswithneovascularisation
AT zhouxun lymphaticvesselsidentifiedinfailedcornealtransplantswithneovascularisation
AT glinkayelena lymphaticvesselsidentifiedinfailedcornealtransplantswithneovascularisation
AT girardeileen lymphaticvesselsidentifiedinfailedcornealtransplantswithneovascularisation
AT yucelyeni lymphaticvesselsidentifiedinfailedcornealtransplantswithneovascularisation
AT guptaneeru lymphaticvesselsidentifiedinfailedcornealtransplantswithneovascularisation