Our aim was to examine for structural and phenotypic evidence of a lymphatic system in the human choroid and to provide the first details of its development using more recently available lymphatic specific markers on choroidal whole mounts and sections. Transmission electron microscopy provided ultrastructural confirmation of a system of lymphatic-like structures within the human choroid and an estimate of the relative frequency of these structures compared to blood vessels in adult human choroid. The classical concept of lymphatics refers to structures that represent blind-ending capillaries building a netlike framework throughout the tissue, converging to larger lymphatic vessels and collector vessels, eventually entering lymph nodes.
21 While we were able to demonstrate the presence of blind-ended lymphatic capillary sacs just external to the choriocapillaris, we were only able to demonstrate limited larger lymphatic channels using recognized lymphatic markers. However, we were able to discriminate lymphatic channels in the outer human choroid using TEM. Similarly to Schroedl et al.,
8 who reported LYVE-1
+ “netlike structures with a pseudovessel-like appearance,”
(p5226) we also recognized very fine, netlike CD34
+/VEGFR-3
+ structures in developing choroid, along with tube-like D2-40
+/collagen IV
−/UEA lectin
− structures in aged choroid. Further, Schroedl et al.
8 noted that “by virtue of their tubular processes, some structures appeared lymphatic-like at a first glance, they neither converged nor formed larger compounds in the periphery.”
(p5226) Our netlike structures and formed lymphatic channels, when observed in nonpathological eyes, predominated in the choroid in regions adjacent to the ONH, but like Schroedl et al.
8, we could not track continuous lymphatic channels using immunohistochemical markers. Further, our findings are consistent with those of Cursiefen and Schroedl (unpublished observations, 2006), referred to in Schroedl et al.,
8 who reported that it was possible to identify lymphatic vessel-like structures with a clear vessel lumen in fetal human eyes. Our previously unpublished observations (Chan-Ling T, et al.
IOVS 2013;54;ARVO E-Abstract D0348) lead us to suggest that in disease conditions involving inflammation and cancer, the larger lymphatic collector channels are more numerous and have a larger lumen diameter. These could be the wispy, netlike structures we observed in deeper choroid in development (
Figs. 2J–L), that have become engorged and may respond to inflammatory stimuli as shown in tissue from a cancer (
Figs. 2M–O) and a T1D patient (
Figs. 3A–O). However, this requires significant further study in order to be substantiated.