Use of the Cornea to Assay for Angiogenic Activity

Abstract

A major difficulty facing investigators of angiogenesis has been the lack of a specific, sensitive, in vivo bioassay system for angiogenic factors. A wide variety of systems have been used in assays for angiogenic factors. These include implantations into rabbit ear chambers (138,659,815), hamster cheek pouch chambers (416,674), the chick chorioallantoic membrane (CAM) (23,33,44,223,241,482,642,686,757), the rat kidney capsule (336,623), polyester sponges (10), healing rabbit bone grafts (154,200), the subcutaneous air “pouch” of Selye (625,626,643), epididymal fat pads seeded onto confluent cultures of myofibroblastic cells (660) as well as the subcutaneous implantation of polyvinyl alcohol sponge discs (211,821) or alginate beads containing sequestered cells (602). Vascular endothelial cell cultures derived from different sources have also been used to assess cell replication, DNA synthesis, cell migration, capillary-like tubular structure formation (239,821) as well as other cellular responses to putative angiogenic and anti-angiogenic factors. All of these methods suffer from significant shortcomings not the least of which is a difficulty in quantitation. Assay systems that involve cultured vascular endothelial cells also pose major problems. Because endothelial cells represent a heterogeneous population (210) the responses by certain endothelial cells to biologically active substances may not necessarily reflect reactions of the microvasculature from which new blood vessels arise.