Abstract: A synthetic truncated norrin protein is provided. The synthetic truncated norrin protein is a ?24 residue N-terminus norrin truncate relative to SEQ ID. NO. 1 that retains the cysteine-knot motif and frizzled-4 binding properties and has a mutation in the cysteine-knot motif in at least one position 81-90 of SEQ ID. NO. 1 that interferes with protease cleavage of the resulting protein thereby extending the biological half-life thereof in vivo relative to native norrin.

Abstract: A method for determining the necessity of a pre-term birth treatment is provided based on obtaining a biological sample from a subject. The biological sample is analyzed for the presence of (P33S;P168S) Frizzled4 (Fzd4) gene variation. The subject or a fetus thereof is then treated for a proclivity to pre-term birth. The Fzd4 protein itself can also be analyzed for the (P33S;P168S) Fzd4 mutation.

Abstract: A method of tightening inter-cellular junctions in endothelial or epithelial cells includes exposing the endothelial or epithelial cells to a norrin in concert with an anti-VEGF agent. Upon sufficient contact time, for norrin to selectively up-regulate gene expression of Cadherin or claudin-5 in the endothelial or epithelial cells, the inter-cellular junctions are tightened.

Abstract: A method of tightening inter-cellular junctions in retinal or choroidal vessel cells includes exposing the retinal or choroidal vessel cells to norrin and an anti-VEGF agent. Upon sufficient contact time, for norrin to selectively up-regulate gene expression of VE-cadherin or claudin-5 in the retinal or choroidal vessel cells, the inter-cellular junctions are tightened. The method is also suitable for treating retinal pigment epithelial cells in wet macular degeneration.

Abstract: A method is provided for capillary stabilization and vascular regeneration in retinal tissue. Capillary regeneration is accomplished with a protein that is a truncated norrin protein (synthetic). The truncated norrin protein has a longer half-life in the eye than native wild norrin proteins. Specific versions of the truncated norrin protein lack a cleavage site that an enzyme in the eye use to cleave to native norrin proteins and thereby shorten the useful life of the protein. The provided method encourages vascular development with an exogenous treatment of truncated norrin that have been investigated in oxygen-induced retinopathy (OIR) mice. The therapeutic feasibility of intravitreal injection of the norrin protein and its effect on retinal development by activating Wnt-signaling has also been shown.

Abstract: A method of tightening inter-cellular junctions in endothelial or epithelial cells includes exposing the endothelial or epithelial cells to norrin. Upon sufficient contact time, for norrin to selectively up-regulate gene expression of Cadherin or claudin-5 in the endothelial or epithelial cells, the inter-cellular junctions are tightened.

Abstract: A method of tightening inter-cellular junctions in retinal or choroidal vessel cells includes exposing the retinal or choroidal vessel cells to norrin. Upon sufficient contact time, for norrin to selectively up-regulate gene expression of VE-cadherin or claudin-5 in the retinal or choroidal vessel cells, the inter-cellular junctions are tightened. The method is also suitable for treating retinal pigment epithelial cells in wet macular degeneration.

Abstract: The invention provides methods, compositions, and kits featuring Wnt signaling enhancing compounds for use in preventing or treating retinal disease.