Abstract: A method for neural regeneration is provided at specific situses that include the inner ear and retina, where Ganglion cells respond to the method through at least stimulation of such cells. As a result, the method provides for reversing clinical conditions associated with the nerve degradation or disease. Specific clinical conditions reversed at least in part through nerve regeneration include hearing loss, tinnitus, and a host of neurotrophic retinopathies, diabetes, Norrie disease, and others. Nerve regeneration is accomplished with a protein that is a truncated synthetic polypeptide related to native norrin protein. Truncated norrin proteins have a longer half-life in the situs than native norrin proteins. A version of the truncated norrin protein lacks a cleavage site for a subject protease enzyme that cleaves native norrin proteins and thereby shortens the useful life of the therapeutic protein.

Abstract: A method is provided to limit inter-cellular leakage between cells in retinal or choroidal vasculature. As a result, an ocular disorder in which ocular or choroidal edema occurs based on leakage of the Adherens Junctions or Tight Junctions is readily treated. The method is particularly well-suited for usage in response to the blood-retinal barrier (BRB) compromise. A method is also provided for the reduction of plasmalemma vesicle-associated protein (PLVAP), which causes transcytosis and pinicytotic leakage. In a particular application, fluid collection under retinal pigment epithelial cells in wet macular degeneration is reduced; a condition currently without effective clinical treatments.

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 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 is provided to increase the expression of the genes CASP3 and THBD; and decrease the expression of the genes COL18A1, CPB2, NPR1, OCLN, BMP2, CLCL6, IL12B, SELPLG, CX3CL1, CASP3, THBD, COL18A1, CPB2, NPR1, CLDN5, CLD3, PIGF, BDNF, CNTF, VEGF-A, CAM-1, PGF, FOX-01, FOX-04, PDGFB, TGFA, HGF, VE-Cadherin, or PLAU. As a result, conditions associated with expression of these genes are treated. Caspase 3 is encoded by CASP3 (GenBank assembly accession: GCA_000001405.22) and cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. Caspase 3 is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease and after spinal cord injury. As caspase 3 is implicated in apoptosis upregulation of CASP3 can be used to induce dysfunction cell removal.

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 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 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 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: 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: An automated method for diagnosing and evaluating severity of retinopathy of prematurity in a retina of a patient is provided that is superior to conventional techniques. A graphical user interface (GUI) is provided for receiving biographical information for the patient creating a patient record in a database via the GUI. A photograph of the retina of the patient is collected and placed in the patient record via the GUI. The photograph is then analyzed to determine vascular distributions within the retina. A zone 1 boundary is assigned to the retina based on a set of threshold levels with respect to the determined vascular distributions. A system for performing the automated method is also provided.

Abstract: A method of tightening inter-cellular junctions in endothelial or epithelial cells includes exposing the endothelial or epithelial cells 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: An automated method for diagnosing and evaluating severity of retinopathy of prematurity in a retina of a patient is provided that is superior to conventional techniques. A graphical user interface (GUI) is provided for receiving biographical information for the patient creating a patient record in a database via the GUI. A photograph of the retina of the patient is collected and placed in the patient record via the GUI. The photograph is then analyzed to determine vascular distributions within the retina. A zone 1 boundary is assigned to the retina based on a set of threshold levels with respect to the determined vascular distributions. A system for performing the automated method is also provided.

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