Norrin regulation of cellular production of junction proteins and use to treat retinal vasculature edema

A method of treating edema in a retina of a living subject by tightening inter-cellular junctions in retinal vessel cells or choroidal vessel cells defining a tissue comprising:

• administering to an eye containing the retinal vessel cells or the choroidal vessel cells an effective amount of an N-terminus norrin truncate having a polypeptide N-terminus cleavage relative to a native norrin protein of a maximum of 40 amino acid residues and retaining a cysteine-knot motif of the native norrin, or a norrin mutant that has at least 85% amino acid identity to SEQ. ID. NO. 1 and retains the cysteine-knot motif of the native norrin;
• administering in concert with said norrin to the eye containing the retinal vessel cells or the choroidal vessel cells an effective amount an anti-VEGF agent selected from the group consisting of:
• bevacizumab, ranibizumab, lapatinib, sunitinib, sorafenib, axitinib, pazopanib, or a combination thereof;
• and
• allowing sufficient time for said norrin to selectively up-regulate gene expression of VE-cadherin and claudin-5 in the retinal vessel cells or the choroidal vessel cells to tighten the inter-cellular junctions of the tissue for prevention of vascular leakage or repair of the vascular leakage to treat the edema in the retina and said anti-VEGF agent to simultaneously suppress VEGF binding to the retinal vessel cells or the choroidal vessel cells.