ENDOTHELIUM MITOGEN IN RETINA--STRUCTURE AND APPLICATION

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The objective of this project is directed through two stages of studies with an ultimate goal of developing methods of inhibiting retinal neovascularization. The scope of the present proposal (Stage I) focuses on investigation of the molecular structure of the specific vascular endothelium mitogens in retina. The specific aims include: purification and characterization of the specific vascular endothelium mitogen(s) from fetal bovine retina. The study, if successful, will provide a chemical basis for the preparation of endothelium mitogen analogs and endothelium mitogen antibodies in the future (Stage II) for a number of investigations dealing with the mechanism of vascular endothelial proliferation and inhibition of retinal neovascularization. Vascular endothelial proliferation is one of the major events in the retinal neovascularization process. Investigations concerned with vascular endothelial proliferation can be performed independently without knowledge of the precise mechanism of the retinal neovascularization process. Unlike programs involving the entire process of retinal neovascularization, experiments on vascular endothelial proliferation are more narrowly focused. In addition, this experimental approach will enable investigators to more effectively design their experiments and interpret their data. Furthermore, success of the present proposal may advance new approaches to this timely investigation. Studies in our and other laboratories indicate that the vascular endothelium mitogen(s) is a protein. Therefore, the experiments of this project are essentially within the scope of our present knowledge of protein chemistry. The purification experiments will include: high performance liquid chromatography; thin-layer peptide mapping; and ion-exchange, metal chelate affinity, and heparin affinity chromatographies. The purified peptide will be analyzed for metal ion content, amino acid composition, N- and C- termini, and molecular weight. Peptide sequence will be performed, if feasible.