Peptides useable for treatment of disorders of the eye
Compounds comprising R-G-Cysteic Acid (i.e., R-G-NH—CH(CH 2 —SO 3 H)COOH or Arg-Gly-NH—CH(CH 2 —SO 3 H)COOH) and derivatives thereof, including pharmaceutically acceptable salts, hydrates, stereoisomers, multimers, cyclic forms, linear forms, drug-conjugates, pro-drugs and their derivatives. Also disclosed are methods for making and using such compounds including methods for inhibiting cellular adhesion to RGD binding sites or delivering other diagnostic or therapeutic agents to RGD binding sites in human or animal subjects.
1. A method for treating a disorder selected from: retinopathy, diabetic retinopathy, macular hole, vitreomacular traction, age related macular degeneration, wet macular degeneration, retinal neovascularization; retinal neovascularization due to diabetic retinopathy and retinal neovascularization due to retinal vein occlusion, in an eye of a subject who suffers from said disorder, said method comprising administering to the subject an effective amount of a compound which comprises Glycinyl-Arginyl-Glycinyl-Cysteic acid-Threonyl-Proline-COOH (SEQ ID NO: 2) or which has the formula:
X1-R-G-Cysteic Acid-X
where X and X1 are selected from: Phe-Val-Ala, -Phe-Leu-Ala, -Phe-Val-Gly, -Phe-Leu-Gly, -Phe-Pro-Gly, -Phe-Pro-Ala, -Phe-Val; or from Arg, Gly, Cysteic acid, Phe, Val, Ala, Leu, Pro, Thr and salts, and any combinations of any D-isomers and L-isomers thereof.
2. A method according to claim 1 wherein the compound comprises SEQ ID NO: 2 and has the structural formula:
3. A method according to claim 1 wherein the compound comprises Glycinyl-Arginyl-Glycinyl-Cysteic acid-Threonyl-Proline-COOH (SEQ ID NO. 2).
4. A method according to claim 1 wherein the disorder causes vitreomacular traction and wherein the administration of the compound deters said vitreomacular traction.
5. A method according to claim 1 wherein the compound is injected into an eye of the subject.
6. A method according to claim 5 wherein the compound is injected intravitreally.
7. A method according to claim 1 wherein the compound is administered topically to an eye of the subject.
8. A method according to claim 7 wherein the compound is contained in a liquid or gel preparation for topical administration to said eye.
9. A method according to claim 1 wherein the compound is administered by intravitreal injection to induce posterior vitreal detachment and/or vitreolysis in the eye prior to performance of a vitrectomy and wherein the method further comprises the step of performing said vitrectomy after the compound has induced said posterior vitreal detachment and/or vitreolysis in the eye.
10. A method according to claim 1 wherein the disorder causes inflammation and wherein the administration of the compound reduces said inflammation.
11. A method according to claim 1 wherein the disorder causes abnormal cell adhesion and wherein the administration of the compound deters said abnormal cell adhesion.
12. A method according to claim 11 wherein the administration of the compound deters adhesion to a cell adhesion motif selected from: fibronectin, vitronectin, laminin, fibrinogen, thrombospondin, and von Willebrand factor.
13. A method according to claim 1 wherein the disorder causes abnormal cellular apoptosis and wherein the administration of the compound reduces said abnormal cellular apoptosis.
14. A method according to claim 1 wherein the disorder causes a pathological integrin-extracellular matrix interaction and wherein the administration of the compound deters said pathological integrin-extracellular matrix interaction.
15. A method according to claim 1 wherein the disorder causes a pathological interaction between fibroblasts and glycoprotein components of extracellular matrix and wherein the administration of the compound deters said pathological interaction between fibroblasts and glycoprotein components of extracellular matrix.
16. A method according to claim 1 wherein the disorder causes abnormal angiogenesis and wherein the administration of the compound reduces said abnormal angiogenesis.