The role of IL ‐6 and IL ‐6‐blockade in the pathogenesis and treatment of uveitic macular edema

Summary Macular edema (ME) is a leading cause of visual loss in uveitis patients. The pathogenesis of uveitic ME includes disruption of tight junction proteins and subsequent breakdown of the blood‐retinal barrier (BRB) that leads to accumulation of fluid within the macular retina. IL‐6 is a pro‐inflammatory cytokine that has been implicated in uveitic ME. Such a notion is supported by clinical cohort studies showing that IL‐6R blockade is beneficial in the treatment of uveitic ME. After studying the clinical efficacy of IL‐6 inhibition in uveitis patients, our group aimed to interrogate the effect of IL‐6 and its blockade with tocilizumab (TCZ) on the barrier properties of an in vitro model of the inner and outer BRB. Our preliminary in vitro data support the hypothesis that IL‐6 disrupts the BRB and contributes to the pathogenesis of ME. Indeed, IL‐6‐induced disrupted ZO‐1 expression was accompanied by an increase in paracellular permeability, and decreased transepitelial electrical resistance (TEER) of ARPE‐19 and human retinal microvascular endotelial cell (HRMEC) monolayers, whereas TCZ‐treated cells could restore IL‐6‐induced barrier disruption.