Editors' ChoiceAngiogenesis

Keeping the Cornea Clear

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Science's STKE  01 Aug 2006:
Vol. 2006, Issue 346, pp. tw258
DOI: 10.1126/stke.3462006tw258

Although parts of the eye are highly vascularized, the ability to see clearly depends on the transparency--and thus the avascularity--of the cornea. Inflammation can promote corneal vascularization. Indeed, trachoma and herpetic keratitis, respectively the leading causes of blindness worldwide and in industrialized nations, are both associated with corneal hemangiogenesis (CHA). A group that previously showed that intact corneal epithelium (the outer layer of the cornea) suppresses CHA investigated the possibility that vascular endothelial growth factor receptor 3 (VEGFR3), which they had found in human corneal epithelial cells, might inhibit inflammatory CHA. Cursiefen et al. used a combination of immunohistochemistry, fluorescence-activated cell sorting (FACS) analysis, and reverse transcription polymerase chain reaction (RT-PCR) to confirm the presence of VEGFR3 on murine corneal epithelial cells (MCEs); further, VEGF-C bound to VEGFR3 on cultured MCEs and stimulated its phosphorylation. After demonstrating that corneal epithelium inhibited CHA following stimuli that elicited an inflammatory response in mouse eyes (corneal cauterization or placement of sutures in the corneal stroma), the authors showed that corneal suturing promoted up-regulation of mRNA encoding the VEGFR3 ligands VEGF-C and VEGF-D. Subconjunctival administration to cauterized de-epithelialized eyes of a chimeric protein containing the mouse VEGFR3 extracellular domain inhibited CHA, whereas the antiangiogenic capacity of corneal epithelium was inhibited by a blocking antibody directed against VEGFR3. Thus, the authors propose that the ectopic expression of VEGFR3 on corneal epithelial cells may act as a trap to keep vascularizing growth factors away from target cells in vascular endothelium.

C. Cursiefen, L. Chen, M. Saint-Geniez, P. Hamrah, Y. Jin, S. Rashid, B. Pytowski, K. Persaud, Y. Wu, J. W. Streilein, R. Dana, Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision. Proc. Natl. Acad. Sci. U.S.A. 103, 11405-11410 (2006). [Abstract] [Full Text]

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