Where and how do leukocytes stall in retinal microcirculation: A spatiotemporal analysis with a focus on junctions...

Irregularities in cellular flow, such as stalls in capillaries, can be potential sources of capillary dysfunction, which significantly impacts oxygen delivery to the central nervous system (CNS). Leukocytes, particularly neutrophils, can act as the stalling elements due to changes in their adhesive or mechanical features. However, the dynamic features of leukocyte stalls in CNS, specifically in the retina, have not been studied in vivo in detail to disclose their association with capillary pericytes and junctions, and their direct influence on red blood cell (RBC) flow. In this study, via in vivo fluorescence microscopy of the retinal capillary network of anesthetized mice and labeling of leukocytes, we characterized the spatiotemporal dynamics of leukocyte travel and their stalls. We found that a significant number of stalls occur at bifurcation points, near pericyte somas, possibly owing to pericytes' impact on capillary tone and geometry. Leukocyte stalls were associated with changes in RBC flow distributions in nearby capillaries. These findings provide insight into the mechanisms and effects of capillary leukocyte stalls, which can help identify the origins of microcirculatory dysfunction in neurological disorders and develop therapeutic strategies targeting leukocytes.