Tumor Growth and Neovascularization: An Experimental Model Using the Rabbit Cornea 2

Abstract

By intracorneal implantation of tumors in the eyes of rabbits, the early neovascular response to solid tumor growth could be directly observed. Fragments of homologous tumors—Brown-Pearce epithelioma and V2 carcinoma—were implanted into the avascular corneal stroma of rabbits at various distances from the limbus. Tumor growth and neovascular response of llmbal vessels were studied by: 1) Slit Lamp Stereomicroscopy, 2) histologic examination, 3) filling of vasculature with colloidal carbon, and 4) autoradiography after exposure to 3Hthymidine. Centrally placed tumors spread as thin plates until they reached within 2.5 ± 0.5 mm of the limbus, when new vessels began to grow from the limbal plexus toward the tumor edge. When tumors became vascularized, they grew rapidly into exophytic masses. Peripherally placed tumors evoked early neovascularization. The prevascular growth of incompatible rabbit homograft and mouse xenograft tumors suggested that the cornea, before its vascularization, was an immunologically privileged site for tumor growth. Intracorneal polyacrylamide gel implants containing tumor extracts elicited a specific pattern of corneal vascularization not observed with nonmalignant cell extracts. These experiments provide a new model for study of tumor growth and neovascularization in a site where there is anatomic separation of tumor cell stimulus from host vascular response; the technique of corneal gel implantation may be useful in the characterization of mediators of neovascularization.