The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration

Loss of the retinal pigment epithelium (RPE) due to dysfunction or disease can lead to blindness in humans. Harnessing the intrinsic ability of the RPE to self-repair is an attractive therapeutic strategy; however, mammalian RPE is limited in its regenerative capacity. Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the RPE, but little is known about the mechanisms that drive RPE regeneration. Here, utilizing zebrafish, we identified elements of the immune response as critical mediators of intrinsic RPE regeneration. Macrophages/microglia are responsive to RPE damage and are required for the timely progression of the regenerative response and our data highlight that inflammation post-RPE injury is also critical for normal RPE regeneration. To our knowledge, these data are the first to identify the molecular and cellular underpinnings of RPE regeneration in any system and hold significant potential for translational approaches aimed towards promoting a pro-regenerative environment in mammalian RPE.