RETINOPATHY TREATMENT: HEPARIN-TARGETED ANTIANGIOGENESIS

PROLIFERATIVE RETINOPATHY, OR OCULAR DISORDERS CHARACTERIZED BY ABNORMAL RETINAL NEOVASCULARIZATION, PRESENTS A SERIOUS CHALLENGE IN OPHTHALMOLOGY. CONVENTIONALTREATMENTS-LASER PHOTOCOAGULATION AND VITRECTOMY-RETARD BUT DO NOT NECESSARILY ABOLISH NEOVASCULARIZATION AND, IN THE PROCESS, PRODUCE SIGNIFICANT SIDE EFFECTS THAT LIMIT THEIR USEFULNESS. IN THE PROPOSED STUDIES, THE CONCEPT OF HEPARIN-TARGETED ANTIANGIOGENESIS WILL BE APPLIED TO THE DESIGN OF DRUGS FOR TREATING PROLIFERATIVE RETINOPATHY. THEPREMISE OF THIS APPROACH IS THAT HEPARIN (OR A HEPARIN FRAGMENT), AS A POTENTIATOR OF ANGIOGENESIS AND ANTIANGIOGENESIS, CAN BE USED AS A DELIVERY VEHICLE FOR DEPOSITING ANGIOGENIC EFFECTORS AT SPECIFIC TARGET CELLS. DURING PHASE I STUDIES, A SERIES OF COVALENT CONJUGATES OF KNOWN ANGIOGENIC EFFECTORS AND HEPARIN (OR HEPARIN FRAGMENTS) WILL BE PREPARED AND TESTED FOR THEIR ANTIANGIOGENESIS THERAPY POTENTIAL. VARIOUS EFFECTORS, SUCH AS A BRAIN-DERIVED ANGIOGENIC POLYPEPTIDE, AN ANGIOGENIC INOSINE DERIVATIVE, AND AN ANGIOSTATIC STEROID, WILL BE COVALENTLY ATTACHED TO HEPARIN (OR HEPARIN FRAGMENTS) USING PUBLISHED PROCEDURES. THE ACTIVITIES OF THE CONJUGATES AS WELL AS APPROPRIATE MIXTURES OF THE CONJUGATE COMPONENTS WILL BE EXAMINED IN AN ANGIOGENESIS ASSAY ON THE CHICKEN CHORIOALLANTOIC MEMBRANE AND IN IN VITRO ASSAYS THAT DISPLAY FEATURES OF THE ANGIOGENESIS PROCESS, NAMELY VASCULAR ENDOTHELIAL CELL MIGRATION AND PROLIFERATION.