The effect of chloroquine on HSV-induced corneal disease - An in vitro and in vivo study

Purpose. To study the effect of chloroquine (CQ) on the development of herpetic ocular Infection. We investigated: (i) HSV-1 mode of entry into corneal fibroblasts and inhibition of this process by CQ; (ii) The effect of CQ on IFN-γ-induced HLA-DR expression in corneal cells; (iii) Therapeutic effect of CQ on herpetic keratitis in rabbits. Methods HSV-1 penetration in cultured Vero and corneal fibroblast cells was evaluated by electron microscopy. HLA-DR antigen in cultured corneal epithelial and fibroblast cells was induced by IFN-γ and analyzed by radioimmunoassay. The effect of CQ on the development of herpetic keratitis was studied in HSV-1 inoculated rabbit eyes (treated topically with or without CQ for 7 days) and evaluated by clinical examinations, histopathology, neutralizing antibodies and virus isolations from tears. Results. HSV-1 penetration into Vero cells occurred (as previously reported) mainly by fusion, while endocytosis was more dominant in corneal fibroblasts (p<0.01). CQ inhibited early steps of viral infection in corneal fibroblasts, but not in Vero cells. CQ also inhibited in a dose-dependent manner IFN-γ-induced expression of HLA-DR antigen in corneal cells. Furthermore, topical CQ treatment moderated the intensity of herpetic corneal disease in rabbit eyes. Conclusions. Endocytosis may play a considerable role in HSV-1 penetration into corneal cells, and is inhibited by CQ. This lysosomotropic agent also inhibits IFN-γ-induced HLA-DR expression on corneal cells. Both processes may contribute to the moderating effect of CQ on HSV-1 infection in rabbit eyes. This study demonstrates the potential of CQ in treatment of herpetic keratitis.