Cyclosporine and neovascularization: Authors’ reply

Abstract

In our model of uveitis, a subcutaneous tuberculin antigen was administered followed by an intravitreal tuberculin challenge approximately 2 weeks later. We believe that the tuberculin antigen initiates an immunologically driven inflammatory response followed by a secondary nonspecific inflammatory response composed of inflammatory cells and soluble inflammatory mediators (e.g., cytokines). Our study did not specifically address the mechanism by which cyclosporine caused corneal neovascularization to regress. However, we believe that the corneal neovascularization most likely resulted from the secondary nonspecific inflammatory response. Cyclosporine could inhibit neovascularization by suppressing the initiating immune-driven inflammatory response. Accordingly, corneal neovascularization is inhibited because the secondary nonspecific inflammatory response is eliminated. Epstein and associates made the interesting observation that systemic cyclosporine inhibited corneal neovascularization initiated by intrastromal IL-2 injection. Similarly, it is likely that cyclosporine inhibited corneal neovascularization induced by nonspecific T-cell inflammatory infiltrate caused by corneal alkali burns (RD Hawkins and associates, 1996, unpublished results). Epstein and colleagues speculated that cyclosporine suppressed T cells to inhibit immunologically mediated neovascularization in their model and in our model. Although it is likely that cyclosporine inhibited an immunologically driven T-cell response, we believe that its effect on corneal neovascularization was a secondary one. In our model of uveitis, a subcutaneous tuberculin antigen was administered followed by an intravitreal tuberculin challenge approximately 2 weeks later. We believe that the tuberculin antigen initiates an immunologically driven inflammatory response followed by a secondary nonspecific inflammatory response composed of inflammatory cells and soluble inflammatory mediators (e.g., cytokines). Our study did not specifically address the mechanism by which cyclosporine caused corneal neovascularization to regress. However, we believe that the corneal neovascularization most likely resulted from the secondary nonspecific inflammatory response. Cyclosporine could inhibit neovascularization by suppressing the initiating immune-driven inflammatory response. Accordingly, corneal neovascularization is inhibited because the secondary nonspecific inflammatory response is eliminated. Epstein and associates made the interesting observation that systemic cyclosporine inhibited corneal neovascularization initiated by intrastromal IL-2 injection. Similarly, it is likely that cyclosporine inhibited corneal neovascularization induced by nonspecific T-cell inflammatory infiltrate caused by corneal alkali burns (RD Hawkins and associates, 1996, unpublished results). Epstein and colleagues speculated that cyclosporine suppressed T cells to inhibit immunologically mediated neovascularization in their model and in our model. Although it is likely that cyclosporine inhibited an immunologically driven T-cell response, we believe that its effect on corneal neovascularization was a secondary one.