Monocyte-derived macrophages promote retinal damage after ischemic stroke via IL-1β-dependent mechanism

Abstract

Vision impairment following ischemic stroke is a prevalent complication that significantly compromises patients' quality of life. Inflammatory responses critically contribute to retinal dysfunction in this condition. Retinal myeloid cells contributed to the retinal inflammatory response, which presented heterogeneity after retinal injury. In this study, we employed the classical middle cerebral artery occlusion (MCAO) mouse model to simulate ischemic stroke. We demonstrated that stroke-induced retinal damage manifests as diminished photoreceptor responses and increased retinal cell apoptosis by using electroretinogram, TdT-mediated dUTP Nick-End Labeling and hematoxylin-eosin staining. Furthermore, we observed myeloid cell infiltration into the retina post-stroke and retinal inflammatory activation after stroke via immunofluorescence staining, retinal bulk RNA sequencing and luminex assay. Through retinal single-cell RNA sequencing, Cx3cr1^GFPCcr2^RFP reporter mice and CCL2 neutralizing antibodies interventions, we observed that infiltrating monocyte-derived macrophages expand and exhibit a predominantly pro-inflammatory phenotype in the retina following stroke. Subsequent experiments utilizing IL-1β neutralizing antibodies and Nlrp3-deficient mice established that IL-1β derived from monocyte-derived macrophages promotes ischemic stroke-induced retinal damage. Collectively, our findings demonstrate that monocyte-derived macrophages drive retinal pathology after ischemic stroke via IL-1β-dependent mechanisms.

Keywords: Interleukin-1β; Ischemic stroke; Monocyte-derived macrophage; Retinal damage.