Norrin regulation of junction proteins and the use thereof to treat epithelial or endothelial membrane leakage induced edema

A method of treating membrane leakage edema in a living subject by tightening inter-cellular junctions in endothelial or epithelial cells to treat membrane leakage induced edema in vivo in a subject comprising:

• administering by subcutaneous injection, intravenous injection, parenteral injection, or intraperitoneal injection an effective amount of an N-terminus norrin truncate that has a polypeptide N-terminus cleavage relative to a native norrin protein of up 40 amino acid residues retaining a cysteine-knot motif of the native norrin and capable of binding to the endothelial or epithelial cells, or a norrin mutant having at least 85% amino acid identity to SEQ ID NO. 1 and retaining a cysteine-knot motif of the native norrin and capable of binding to the endothelial or epithelial cells defining one of:
• a blood vessel, a lymphatic capillary, or a blood-intestinal barrier;
• and
• allowing sufficient time for said N-terminus norrin truncate or said norrin mutant to selectively up-regulate gene expression of Cadherin and claudin-5 in the endothelial or epithelial cells to tighten the inter-cellular junctions of the tissue for prevention of vascular leakage or repair of the vascular leakage to treat the membrane leakage induced edema.