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Impressum
Time-course of pericyte recruitment in human corneal angiogenesis
Cursiefen C., Hofmann-Rummelt C., Schlötzer-Schrehardt U., Küchle M.
Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany
Objective: During angiogenesis, newly sprouted vessels undergo
a period of "pruning" when endothelial cells become apoptotic
if angiogenic factors are lacking. Morphologically, this period correlates
with the absence of pericyte-coverage of new vessels. Mature, pericyte-covered
vessels do not depend on angiogenic factors anymore. Purpose of this study
was to analyze whether and if yes when pathologic vessels in human corneal
neovascularization (CN) acquire pericyte coating. This could be important
for the timing of a corneal antiangiogenic therapy acting by blockage
of angiogenic factors.
Methods: Vascularized human corneas obtained by keratoplasty after
different periods of CN were evaluated by electron microscopy for type,
size and pericyte coverage of new vessels. These data were correlated
with the duration of CN (73±95 months [0.5-360]; n=15). CN was
secondary to herpetic keratitis, transplant insufficiency/rejection, corneal
trauma or aniridia.
Results: Overall, 196 blood vessels were analyzed ultrastructurally:
72 (37%) of blood vessels were classified as capillaries, 122 (62%) as
venules and 2 (1%) as arterioles. Electron microscopically, 170 (87%)
vessels were covered by pericytes and 2 (1%) in addition by smooth muscle
cells. Pericyte recruitment increased with time evolving between onset
of CN and keratoplasty: Three months after initiation of CN, more than
80% of new vessels were covered by pericytes. In corneas without ongoing
inflammation, after 3 years all vessels were covered by pericytes.
Conclusion: Pathologic new vessels in human CN are rapidly covered
by pericytes. Thus only in the very beginning of human CN, antiangiogenic
strategies relying on a blockade of angiogenic factors could lead to blood
vessel regression.
Support: IZKF Erlangen, B13