Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model

Abstract

Subretinal fibrosis has been recognized as a feature of an advanced stage of exudative age-related macular degeneration (AMD) that leads to irreversible loss of vision. This study was aimed at elucidating roles of interlukin-6 (IL-6) in the development of subretinal fibrosis. Immunohistochemistry (IHC) was performed with anti-human IL-6 antibody in surgically excised choroidal neovascular tissues from patients with exudative AMD. The area of subretinal fibrosis was measured in a mouse subretinal fibrosis model with injection of control small interfering RNA(siRNA) or IL-6 siRNA, or isotype control antibody or anti-IL-6 receptor antibody after peritoneal exudative cells (PECs) injection into the vitreous cavity. PECs derived from IL-6+/+ or IL-6−∕− mice were placed into the subretinal space of IL-6+/+ mice. IL-6 was expressed in the stroma and retinal pigment epithelial (RPE) layer in the choroidal neovascular tissues. IL-6 knockdown or blocking of the IL-6 receptor suppressed the formation of subretinal fibroblastic scars. The area of subretinal fibrosis induced by PECs derived from IL-6−∕− mice was less than that induced by PECs from IL-6+/+ mice. The results suggested that IL-6, expressed by activated macrophages, is a crucial mediator that promotes subretinal fibrosis. Targeting IL-6 and the corresponding signaling pathway would be an attractive therapeutic approach not only in choroidal neovascularization, but also in subretinal fibrosis.