Spontaneous lymphatic vessel formation and regression in the murine cornea.
OBJECTIVE
Lymphatic dysfunctions are associated with many diseases, ranging from cancer metastasis to transplant rejection, for which there is little effective treatment. To date, there is no natural model with which to study lymphatic regression. This study was conducted to investigate whether murine cornea, an extensively exploited tissue for vascular studies, derives its lymphatic-free status from a natural regression mechanism. The differential behaviors between the lymphatic and blood vessels under normal development and inflammation conditions are also compared.


METHODS
Normal mouse eyeballs or whole-mount corneas encompassing the entire course of corneal development and maturation and adult inflamed corneas were used for immunofluorescent microscopic studies.


RESULTS
The data demonstrated, for the first time, that mouse cornea was endowed with a significant number of lymphatic vessels that underwent spontaneous formation and regression during a critical period after birth, which was not observed for blood vessels. Because lymphatic growth can be reactivated in the adult cornea after inflammatory stimulation, the cornea thereby becomes the first tissue ever identified to have a full range of lymphatic plasticity.


CONCLUSIONS
These novel findings not only provide a new concept in defining the cornea and its related diseases, they also reveal a completely natural model with which to study both lymphatic regression and formation. It is hoped that further studies will divulge novel and potent pro- or anti-lymphatic factors to treat lymphatic disorders inside and outside the eye.
Zhang
Hui
H
Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California 94720, USA.
Hu
Xuemei
X
Tse
Julie
J
Tilahun
Firehiwott
F
Qiu
Mengsheng
M
Chen
Lu
L
D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000378:metabolism; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D003315:Cornea / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000196:embryology / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007634:Keratitis / Q000378:metabolism; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000196:embryology* / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D000943:Antigens, Differentiation; D006023:Glycoproteins; D018398:Homeodomain Proteins; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C492273:LYVE1 protein, mouse; C036763:monocyte-macrophage differentiation antigen