Disruption of the precise balance of positive and negative molecular regulators of blood and lymphatic vessels can lead to myriad diseases that affect one in four people worldwide. Although dozens of natural inhibitors of hemangiogenesis have been identified, an endogenous selective inhibitor of lymphatic vessels has not yet been described. We report the existence of a secreted, splice variant of vascular endothelial growth factor receptor-2 (sVegfr-2) that inhibits developmental and reparative lymphangiogenesis by blocking Vegf-c. Tissue-specific loss of sVegfr-2 in mice induced, at birth, spontaneous lymphatic invasion of the normally alymphatic cornea and hyperplasia of skin lymphatics without accompanying changes in blood vasculature. sVegfr-2 inhibited lymphangiogenesis but not hemangiogenesis induced by corneal suture injury or transplantation, enhanced corneal allograft survival, and suppressed lymphangioma cellular proliferation. Naturally occurring sVegfr-2 is a molecular uncoupler of blood and lymphatic vessels whose modulation might have a therapeutic role in lymphatic vascular malformations, transplantation, and potentially in tumor lymphangiogenesis and lymphedema.

The findings indicate that cultured HCECs transplanted from adult human donor cornea by means of a collagen sheet can retain their function of corneal dehydration in a rabbit model and suggest the feasibility of transplantation for CEC dysfunction using cultured HCECs with a collagen sheet.

These findings indicate that the HCEC contains precursor cells with a propensity to differentiate into HCECs and that these cells can also produce neuronal and mesenchymal cell proteins.

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