Angiogenesis, the formation of new blood vessels, is a key element of a number of normal and pathological processes. Whereas vascularization is a primary event associated with normal embryogenesis and wound healing, neovascularization is of central importance also n a variety of disease states. Neovascularization in the eye is an almost universal aspect of ocular disease and injury, new blood vessels are associated with immunological reactions and the inflammatory processes, and angiogenesis plays a pivotal role in permitting the growth and differentiation of autochthonous tumors and their metastases. The proposed research is directed at a greater understanding of the process of neovascularization, with special emphasis on lymphocyte-induced angiogenesis. Specifically, the aims of this research include: 1. Identification and characterization of angiogenic lymphokines released by lymphocytes following immune stimulation; 2. Delineation of site-dependent selectivity in the neovascular response as this may be reflected by heterogeneity in the microvascular endothelial cell phenotype; 3. Development and validation of in vitro correlates of angiogenesis and of more quantitative and readily reproducible in vivo tests of neovascular reactions, using the mouse as an animal model. 4. Study of mouse mutants with specific vascular or immunological deficiencies and with cells obtained from those mice, as a means of developing specific disease models applicable to human diseases. Research methods include cell culture analysis of migration and proliferation; flow cytometry and cell sorting; production and testing of monoclonal antibodies against angiogenic lymphokines; biochemical procedures designed for purification of specific angiokines, and image analysis for assessment of new blood vessel formation.
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