Photoreceptor loss does not recruit neutrophils despite strong microglial activation

In response to central nervous system (CNS) injury, tissue resident immune
cells such as microglia and circulating systemic neutrophils are often
first responders. The degree to which these cells interact in response to
CNS damage is poorly understood, and even less so, in the neural retina
which poses a challenge for high resolution imaging in vivo. In this
study, we deploy fluorescence adaptive optics scanning light
ophthalmoscopy (AOSLO) to study microglia and neutrophils in mice. We
simultaneously track immune cell dynamics using label-free phase-contrast
AOSLO at micron-level resolution. Retinal lesions were induced with 488 nm
light focused onto photoreceptor (PR) outer segments. These lesions
focally ablated PRs, with minimal collateral damage to cells above and
below the plane of focus. We used in vivo (AOSLO, SLO and OCT) imaging to
reveal the natural history of the microglial and neutrophil response from
minutes-to-months after injury. While microglia showed dynamic and
progressive immune response with cells migrating into the injury locus
within 1-day after injury, neutrophils were not recruited despite close
proximity to vessels carrying neutrophils only microns away. Post-mortem
confocal microscopy confirmed in vivo findings. This work illustrates that
microglial activation does not recruit neutrophils in response to acute,
focal loss of PRs, a condition encountered in many retinal diseases.