Purchase this article with an account.
Tailoi Chan-Ling, Louise Baxter, Ping Hu, Samuel Adamson, Frank Arfuso, Michele Madigan, Mark Koina; Compelling Evidence Of Lymphangiogenesis And Lymphatic Vessels In The Developing And Adult Human Choroid. Invest. Ophthalmol. Vis. Sci. 2013;54(15):312.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The lymphatic system plays a key role in maintaining fluid homeostasis, macromolecular (including lipid) absorption, immune surveillance & tumour metastasis. Our aim is to provide definitive evidence for lymphatics in human choroid, and to investigate the cellular mechanisms of lymphatic formation.
Choroidal wholemounts & sections from 12-20 weeks gestation & young adult choroids (20-40 yrs) were examined with multiple marker immunohistochemistry (IHC) using PROX-1, LYVE-1, Podoplanin, D-240, endomucin, VEGF-C & VEGF-R3 antibodies. CD34 & CD39 antibodies were also used to co-visualise vascular lineage cells. Ultrastructural criteria & frequency of lymphatics relative to the vascular lineage was determined using TEM.
The processes of vasculogenesis & angiogenesis preceded lymphangiogenesis during formation of human choroid. The topography of lymphatic formation was centred around the optic nerve & showed a distinct optic disc to periphery topography. A subset of CD34+ hematopoietic stem cells (HSCs) were PROX-1+/Podoplanin+/D240+/VEGF-R3+ & likely represent lymphatic precursor cells (LPCs). These presumed LPCs were distributed as single cells during embryological development. PROX-1+/LYVE-1+/D-240+/VEGF-R3+ macrophages were frequently associated with forming lymphatic channels. Numerous blind ended lymph sacs just external to the choriocapillaris were evident utilizing VEGFR-3/CD34/D-240/LYVE-1 multiple marker IHC. The presence of mid-sized & larger lymphatic channels was determined using both ultrastructural criteria & IHC on choroidal wholemounts. Ultrastructural features of lymphatics included presence of; anchoring filaments, flocculent protein within lymphatic lumina but absence of RBCs; high endothelial cells; incomplete basal lamina; absence of pericytes and double-layered vessel walls and branch patterns typical of lymphatics. In healthy young adults, the relative frequency of lymphatic channels compared to capillaries, arterioles and arteries was 7%, 1% and 5% respectively based on ultrastructural criteria.
Our finding of a system of blind-ended lymphatic capillaries just external to the choriocapillaris places them in an ideal position to subserve their functions of fluid homeostasis, macromolecular absorption and immune surveillance for the choroid. Their existence in the human choroid has major implications for pathogenesis of ARMD, DR & myopia.
This PDF is available to Subscribers Only