Abstract: A method of preserving cone cells in the eye of a mammal suffering from a retinal degenerative disease comprises isolating from the bone marrow of the mammal a lineage negative hematopoietic stem cell population that includes endothelial progenitor cells, transfecting cells from the stem cell population with a gene that operably encodes an antiangiogenic fragment of human tryptophanyl tRNA synthetase (TrpRS), and subsequently intravitreally injecting the transfected cells into the eye of the mammal in an amount sufficient to inhibit the degeneration of cone cells in the retina of the eye. The treatment may be enhanced by stimulating proliferation of activated astrocytes in the retina using a laser.

Abstract: The invention provides an isolated nucleic acid encoding a polypeptide capable of inhibiting angiogenesis or neovascularization, wherein the nucleic acid comprises a first polynucleotide sequence comprising a coding sequence at least 95 percent identical to a sequence selected from the group consisting of a polynucleotide SEQ ID NO:6, a polynucleotide that encodes a polypeptide of SEQ ID NO:12, and a polynucleotide that encodes a fragment of the polypeptide of SEQ ID NO:12; and wherein the nucleic acid does not encode for the amino acid sequence of amino acids 71-93 of SEQ ID NO:1. Pharmaceutical compositions, vectors, and methods for inhibiting neovascularization or angiogenesis comprising or utilizing the nucleic acids also are provided.

Abstract: The invention provides an isolated nucleic acid encoding a polypeptide capable of inhibiting angiogenesis or neovascularization, wherein the nucleic acid comprises a first polynucleotide sequence comprising a coding sequence at least 95 percent identical to a sequence selected from the group consisting of a polynucleotide SEQ ID NO:6, a polynucleotide that encodes a polypeptide of SEQ ID NO:12, and a polynucleotide that encodes a fragment of the polypeptide of SEQ ID NO:12; and wherein the nucleic acid does not encode for the amino acid sequence of amino acids 71-93 of SEQ ID NO:1. Pharmaceutical compositions, vectors, and methods for inhibiting neovascularization or angiogenesis comprising or utilizing the nucleic acids also are provided.

Abstract: An isolated peptide useful as a selective antagonist of mammalian R-cadherin comprises 3 to 30 amino acid residues, three contiguous residues of the peptide having the amino acid sequence Ile-Xaa-Ser; wherein Xaa is an amino acid residue selected from the group consisting of Asp, Asn, Glu, and Gln. Preferably Xaa is Asp or Asn. In one preferred embodiment the peptide is a cyclic peptide having 3 to 10 amino acid residues arranged in a ring. The selective R-cadherin antagonist peptides of the invention are useful for inhibiting the targeting of stem cells, such as endothelial precursor cells, to developing vasculature, for inhibiting R-cadherin mediated cellular adhesion, and for inhibiting retinal angiogenesis.

Abstract: The invention provides methods of using isolated monocyte populations to treat subjects suffering from various ocular vascular disease or ocular degenerative disorders. The present invention also provides novel methods for isolating substantially pure monocyte populations. The methods involve extracting a blood sample or a bone marrow sample from a subject, debulking red blood cells from the sample, and then separating remaining red blood cells and other cell types in the sample from monocytes. Instead of using any selection or labeling agents, the red blood cells and other cell types are separated from monocytes based on their size, granularity or density. The isolated monocytes can be further activated in vitro or ex vivo prior to being administered to a subject. Isolated cell populations containing substantially pure CD14+/CD33+ monocytes are also provided in the invention.

Abstract: The invention provides a method for inhibiting ocular neovascularization in a patient. The method comprises administering to a patient an ocular neovascularization inhibiting amount of a water-soluble polypeptide selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 7, and an ocular neovascularization inhibiting fragment thereof, which includes at least one of amino acid residue signature sequences HVGH (SEQ ID NO:10) and KMSAS (SEQ ID NO:11). A method for assaying the angiogenesis inhibiting activity of a composition is also provided.

Abstract: The present invention provides an isolated myeloid-like bone marrow cell population comprising a majority of cells that are lineage negative, and which express both CD44 antigen and CD11b antigen. These cells have beneficial vasculotrophic and neurotrophic activity when intraocularly administered to the eye of a mammal, particularly a mammal suffering from an ocular degenerative disease. The myeloid-like bone marrow cells are isolated by treating bone marrow cells with an antibody against CD44 (hyaluronic acid receptor), against CD11b, or against both and using flow cytometry to positively select CD44 and/or CD11b expressing cells therefrom. The isolated myeloid-like bone marrow cells of the invention can be transfected with a gene encoding a therapeutically useful protein, for delivering the gene to the retina.

Abstract: Isolated, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin? HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye. Preferably at least about 20% of the cells in the isolated Lin? HSCs express the cell surface antigen CD31. The isolated Lin? HSC populations are useful for treatment of ocular vascular diseases. In a preferred embodiment, the Lin? HSCs are isolated by extracting bone marrow from an adult mammal; separating a plurality of monocytes from the bone marrow; labeling the monocytes with biotin-conjugated lineage panel antibodies to one or more lineage surface antigens; removing of monocytes that are positive for the lineage surface antigens from the plurality of monocytes, and recovering a Lin? HSC population containing EPCs.

Abstract: The present invention provides an isolated myeloid-like cell population comprising a majority of cells that are lineage negative, and which express both CD44 antigen, CD11b antigen, and hypoxia inducible factor 1 ? (HIF-1 ?). These cells have beneficial vasculotrophic and neurotrophic activity when intraocularly administered to the eye of a mammal, particularly a mammal suffering from an ocular degenerative disease. The myeloid-like cells are isolated by treating bone marrow cells, peripheral blood cells or umbilical cord cells with an antibody against CD44 (hyaluronic acid receptor), against CD11b, CD14, CD33, or against a combination thereof and using flow cytometry to positively select CD44 and/or CD11b expressing cells therefrom. The isolated myeloid-like bone marrow cells of the invention can be transfected with a gene encoding a therapeutically useful protein, for delivering the gene to the retina.

Abstract: Isolated, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin? HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye. Preferably at least about 20% of the cells in the isolated Lin? HSCs express the cell surface antigen CD31. The isolated Lin? HSC populations are useful for treatment of ocular vascular diseases and to ameliorate cone cell degeneration in the retina. In a preferred embodiment, the Lin? HSCs are isolated by extracting bone marrow from an adult mammal; separating a plurality of monocytes from the bone marrow; labeling the monocytes with biotin-conjugated lineage panel antibodies to one or more lineage surface antigens; removing of monocytes that are positive for the lineage surface antigens from the plurality of monocytes, and recovering a Lin? HSC population containing EPCs. The isolated Lin? HSCs also can be transfected with therapeutically useful genes.

Abstract: Isolated, mammalian, adult bone marrow-derived, lineage negative hematopoietic stem cell populations (Lin? HSCs) contain endothelial progenitor cells (EPCs) capable of rescuing retinal blood vessels and neuronal networks in the eye. Preferably at least about 20% of the cells in the isolated Lin? HSCs express the cell surface antigen CD31 and not more than about 1 percent of the cells express Tie-2. The isolated Lin? HSC populations are useful for treatment of ocular vascular diseases.

Abstract: The present invention provides a method of rebuilding and stabilizing functional vasculature in hypoxic retinal tissue comprising contacting the hypoxic retinal tissue with an effective amount of cells from an isolated myeloid-like cell population comprising a majority of cells that express CD44 antigen, CD11b antigen, and hypoxia inducible factor 1? (HIF-1?). The isolated myeloid-like bone marrow cells optionally can be transfected with a gene encoding a therapeutically useful peptide, for delivering the gene to the retina.

Abstract: Methods and compositions for prophylaxis and/or treatment of diseases of the eye of a patient resulting angiogenesis in the eye using antagonists of the integrin receptors ?v ?3 and/or ?v ?5. The compositions can be nanoparticles and are administered to the eye by injection into the sclera of the eye.

Abstract: Methods for the treatment of a disease of the eye of a patient comprising injecting into the vitreous body of the eye a composition comprising a therapeutically effective amount of an ?v?3 and/or ?v?5 inhibitor sufficient to inhibit angiogenesis and inhibit neovascularization in the treated eye. The ?v?3 and/or ?v?5 inhibitor being a compound of formula II: as defined herein or a physiologically acceptable salt thereof.

Abstract: The present invention provides compositions and methods of treating neovascular diseases, such as a retinal neovascular diseases and tumors, by administering to a patient suffering from a neovascular disease or tumor a vascular development inhibiting amount of a combination of the angiogenesis suppressing drugs comprising an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one compound selected from the group consisting of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor. Compositions for use in the methods include an admixture of an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor, together with a pharmaceutically acceptable excipient.

Abstract: The invention provides a method for inhibiting ocular neovascularization in a patient. The method comprises administering to a patient an ocular neovascularization inhibiting amount of a water-soluble polypeptide selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 7, and an ocular neovascularization inhibiting fragment thereof, which includes at least one of amino acid residue signature sequences HVGH (SEQ ID NO:10) and KMSAS (SEQ ID NO:11).

Abstract: An isolated peptide useful as a selective antagonist of mammalian R-cadherin comprises 3 to 30 amino acid residues, three contiguous residues of the peptide having the amino acid sequence Ile-Xaa-Ser; wherein Xaa is an amino acid residue selected from the group consisting of Asp, Asn, Glu, and Gln. Preferably Xaa is Asp or Asn. In one preferred embodiment the peptide is a cyclic peptide having 3 to 10 amino acid residues arranged in a ring. The selective R-cadherin antagonist peptides of the invention are useful for inhibiting the targeting of stem cells, such as endothelial precursor cells, to developing vasculature, for inhibiting R-cadherin mediated cellular adhesion, and for inhibiting retinal angiogenesis.

Abstract: The present invention provides compositions and methods of treating neovascular diseases, such as a retinal neovascular diseases and tumors, by administering to a patient suffering from a neovascular disease or tumor a vascular development inhibiting amount of a combination of the angiogenesis suppressing drugs comprising an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one compound selected from the group consisting of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor. Compositions for use in the methods include an admixture of an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor, together with a pharmaceutically acceptable excipient.

Abstract: The invention provides a method for inhibiting ocular neovascularization in a patient. The method comprises administering to a patient an ocular neovascularization inhibiting amount of a water-soluble polypeptide selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 7, and an ocular neovascularization inhibiting fragment thereof, which includes at least one of amino acid residue signature sequences HVGH (SEQ ID NO:10) and KMSAS (SEQ ID NO:11). A method for assaying the angiogenesis inhibiting activity of a composition is also provided.

Abstract: The present invention provides a method for treating retinopathy of prematurity (ROP) and related retinopathic diseases. The method comprises administering to the retina of a mammal suffering from, or at risk of developing, retinopathy of prematurity or a related retinopathic disease an amount of cells from a vasculotrophic lineage negative hematopoietic stem cell population, effective to promote beneficial physiological revascularization of damaged areas of the retina and to ameliorate damage to the retina caused by the disease. Preferably, the mammal is a human patient. In one preferred embodiment, the lineage negative hematopoietic stem cell population is a lineage negative hematopoietic stem cell population comprising hematopoietic stem cells and endothelial progenitor cells (i.e., Lin? HSC).