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S. Fickenscher, C. Rummelt, F. Kruse, W. Neuhuber, F. Schroedl, C. Cursiefen; Corneal Angiogenic Privilege During Development . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1651.
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Whether "corneal angiogenic privilege" already exists in utero during development was so far unknown. Here we analyze whether the normal human cornea is primarily devoid of both blood and lymphatic vessels during intrauterine development or whether secondary regression of pre–existing vessels occurs prior to delivery.
Indirect double–immunohistochemistry was performed on 5 µm serial pupil–optic disc sections of paraffin–embedded human eyes stillborn at gestational ages of 15 – 41 weeks with antibodies against vWF (von Willebrand factor; factor VIII–associated antigen) as a panendothelial marker and with antibodies against LYVE–1 (lymphatic vessel endothelial hyaluronate receptor 1) as a specific marker for lymphatic vascular endothelium. In addition, routine histology using H&E and PAS staining was performed and cornea and adjacent conjunctiva were evaluated.
The human cornea was devoid of both vWF+/LYVE–1– blood vessels as well as vWF+/LYVE–1+ lymphatic vessels at all time points analyzed. In contrast, there were numerous blood and lymphatic vessels detectable in the subconjunctival space during development. Furthermore, non–regressed blood vessels around the lens were present. Antiangiogenic factors such as Endostatin were already expressed in the developing cornea.
The normal fetal human cornea is primarily avascular and devoid of both blood and lymphatic vessels. Corneal angiogenic privilege is already achieved very early during intrauterine development. This suggests early and strong expression of both antiangiogenic and antilymphangiogenic factors in the human cornea during development.
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